The present invention relates to a novel fused ring compound and a pharmaceutically acceptable salt thereof useful as a therapeutic agent for hepatitis C, and to an intermediate compound for the synthesis thereof. The present invention also relates to a novel use of a certain fused ring compound or a pharmaceutically acceptable salt thereof as a therapeutic agent for hepatitis C. More particularly, the present invention relates to a therapeutic agent for hepatitis C, which contains a novel fused ring compound or a pharmaceutically acceptable Salt thereof, which is effective for the prophylaxis or treatment of hepatitis C and which shows anti-hepatitis C virus (HCV) activity, particularly anti-HCV activity based on an RNA-dependent RNA polymerase inhibitory activity.
In 1989, a main causative virus of non-A non-B posttransfusion hepatitis was found and named hepatitis C virus (HCV). Since then, several types of hepatitis viruses have been found besides type A, type B and type C, wherein hepatitis caused by HCV is called hepatitis C.
The patients infected with HCV are considered to involve several percent of the world population, and the infection with HCV characteristically becomes chronic.
HCV is an envelope RNA virus, wherein the genome is a single strand plus-strand RNA, and belongs to the genus Hepacivirus of Flavivirus (from The International Committee on Taxonomy of Viruses, International Union of Microbiological Societies). Of the same hepatitis viruses, for example, hepatitis B virus (HBV), which is a DNA virus, is eliminated by the immune system and the infection with this virus ends in an acute infection except for neonates and infants having yet immature immunological competence. In contrast, HCV somehow avoids the immune system of the host due to an unknown mechanism. Once infected with this virus, even an adult having a mature immune system frequently develops persistent infection.
When chronic hepatitis is associated with the persistent infection with HCV, it advances to cirrhosis or hepatic cancer in a high rate. Enucleation of tumor by operation does not help much, because the patient often develops recurrent hepatic cancer due to the sequela inflammation in non-cancerous parts.
Thus, an effective therapeutic method of hepatitis C is desired. Apart from the symptomatic therapy to suppress; inflammation with an anti-inflammatory agent, the development of a therapeutic agent that reduces HCV to a low level free from inflammation and that eradicates HCV has been strongly demanded.
At present, a treatment with interferon is the only effective method known for the eradication of HCV. However, interferon can eradicate the virus only in about one-third of the patient population. For the rest of the patients, it has no effect or provides only a temporary effect. Therefore, an anti-HCV drug to be used in the place of or concurrently with interferon is awaited in great expectation.
In recent years, Ribavirin (1-xcex2-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) has become commercially available as a therapeutic agent for hepatitis C, which is to be used concurrently with interferon. It enhances the efficacy of interferon but only to a low efficacy rate, and a different novel therapeutic agent for hepatitis C is desired.
Also, an attempt has been made to potentiate the immunocompetence of the patient with an interferon agonist, an interleukin-12 agonist and the like, thereby to eradicate the virus, but an effective pharmaceutical agent has not been found yet.
In addition, the inhibition of HCV growth, wherein HCV-specific protein is targeted, has been drawing attention these days.
The gene of HCV encodes a protein such as serine protease, RNA helicase, RNA-dependent RNA polymerase and the like. These proteins function as a specific protein essential for the growth of HCV.
One of the specific proteins, RNA-dependent RNA polymerase (hereinafter to be also briefly referred to as an HCV polymerase), is an enzyme essential for the growth of the virus. The gene replication of HCV having a plus-strand RNA gene is considered to involve synthesis of a complementary minus-strand RNA by the use of the plus-strand RNA as a template, and, using the obtained minus-strand RNA as a template, amplifying the plus-strand RNA. The portion called NS5B of a protein precursor, that HCV codes for, has been found to show an RNA-dependent RNA polymerase activity (EMBO J., 15, 12-22, 1996), and is considered to play a central role in the HCV gene replication.
Therefore, an HCV polymerase inhibitor can be a target in the development of an anti-HCV drug, and the development thereof is eagerly awaited. However, an effective HCV polymerase inhibitor has not been developed yet, like in other attempts to develop an anti-HCV drug based on other action mechanisms. As the situation stands, no pharmaceutical agent can treat hepatitis C satisfactorily.
The following discloses known compounds relatively similar to the compound of the present invention.
A known therapeutic agent for hepatitis C having a benzimidazole skeleton is disclosed in WO97/36866, Japanese Patent Application under PCT laid-open under kohyo No. 2000-511899 (EP906097) and WO99/51619.
WO97/36866 discloses the following compound D and the like, and HCV helicase inhibitory activity of the compounds.
Japanese Patent Application under PCT laid-open finder kohyo No. 2000-511899 (EP906097) discloses the following compound E and the like, and WO99/51619 discloses the following compound F and the like, in both of which a possibility of these compounds being effective as an HCV inhibitor is mentioned.
However, these publications do not include the compound disclosed in the present specification, or a disclosure suggestive thereof. 
A known anti-hepatitis virus agent having a benzimidazole skeleton is disclosed in Japanese Patent Application under PCT laid-open under kohyo No. 2000-503017 (WO97/25316) and Japanese Patent Application under PCT laid-open under kohyo No. 0-505092 (WO96/7646)
WO97/25316 discloses the following compound A and the like, wherein the use thereof is for a treatment of viral infection. The target virus is a DNA virus such as hepatitis B virus and the like. However, this publication does not include the compound disclosed in the present specification or a description regarding or suggestive of HCV.
Japanese Patent Application under PCT laid-open under kohyo No. 10-505092 discloses the following compound B and the like, wherein the use thereof is for a treatment of viral infection. The target virus is a DNA virus such as herpesvirus and hepatitis B virus. However, this publication does not include the compound disclosed in the present specification or a description regarding or suggestive of HCV. 
The benzimidazole derivatives having an antiviral activity have been disclosed in JP-A-3-31264, U.S. Pat. No. 3,644,382 and U.S. Pat. No. 3,778,504. In addition, WO98/37072 discloses, as a production inhibitor of tumor necrosis factor (TNF) and cyclic AMP, a benzimidazole derivative for the use as an anti-human immunodeficiency virus (HIV) agent and an anti-inflammation agent. WO98/05327 discloses, as a reverse transcriptase inhibitor, a benzimidazole derivative for the use as an anti-HIV agent. J. Med. Chem. (13(4), 697-704, 1970) discloses, as a neuraminidase inhibitor, a benzimidazole derivative for the use as an anti-influenza virus agent.
However, none of these publications includes the compound of the present invention or a description regarding or suggestive of an anti-HCV effect.
Known benzimidazole derivatives having a pharmaceutical use other than as an antiviral agent are disclosed in JP-A-8-501318 (U.S. Pat. No. 5,814,651) and JP-A-8-134073 (U.S. Pat. No. 5,563,143). These publications disclose the following compound C and the like as a catechol diether compound, and the use thereof as an anti-inflammation agent. However, neither of the publications includes the compound of the present invention, and as the action mechanism, the former discloses phosphodiesterase IV and the latter discloses TNF. These publications do not include a description regarding or suggestive of an anti-HCV effect.
Japanese Patent Application under PCT laid-open under kohyo No. 2000-159749 (EP882718) discloses the following compound G and the like, and the use thereof for the treatment of bronchitis, glomerulonephritis and the like. However, this publication does not include the compound of the present invention, but discloses only a phosphodiesterase IV inhibitory and hypoglycemic action. This publication does not include a description regarding or suggestive of an anti-HCV effect.
U.S. Pat. No. 6,211,177 discloses the following compound H and the like with their use as antitumor agents. However, this publication does not encompass the compound of the present invention, and does not disclose or suggest an anti-HCV effect. 
WO98/50029, WO98/50030 and WO98/50031 disclose benzimidazole derivatives as an antitumor agent having a protein isoprenyl transferase action. While this publication discloses a wide scope of the claims, at least it does not include a compound analogous to the compound of the present invention or a description regarding or suggestive of an anti-HCV effect.
JP-A-8-109169 (EP694535) discloses the application of a tachykinin receptor antagonist to treat an inflammatory disease, and WO96/35713 discloses the application thereof as a growth hormone release promoter to treat a growth hormone-related disease such as osteoporosis and the like. However, none of these publications includes a description regarding or suggestive of an anti-HCV effect.
WO2001/21634 discloses the following compound I in a chemical library. However, this publication does not encompass the compound of the present invention. While it discloses an antimicrobial activity of certain compounds, this publication does not teach or suggest an anti-HCV effect. 
JP-A-53-14735 discloses a benzimidazole derivative as a brightener besides its pharmaceutical use, but this publication does not include the compound of the present invention.
Based on the findings from the preceding studies, it has been elucidated that a pharmaceutical agent having an anti-HCV activity is effective for the prophylaxis and treatment of hepatitis C, and particularly an anti-HCV agent having fin inhibitory activity on RNA-dependent RNA polymerase of HCV can be a prophylactic and therapeutic agent effective against hepatitis C and a prophylactic and therapeutic agent for the disease caused by hepatitis C.
Accordingly, the present invention provides a pharmaceutical agent having an anti-HCV activity, particularly a pharmaceutical agent having an RNA-dependent RNA polymerase inhibitory activity.
The present inventors have made an in-depth study of compounds having an anti-HCV activity, particularly RNA-dependent RNA polymerase inhibitory activity, and completed the present invention.
Thus, the present invention provides the following (1) to (117).
(1) A therapeutic agent for hepatitis C, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient: 
wherein
a broken line is a single bond or a double bond,
G1 is C(xe2x80x94R1) or a nitrogen atom,
G2 is C(xe2x80x94R2) or a nitrogen atom,
G3 is C(xe2x80x94R3) or a nitrogen atom,
G4 is C(xe2x80x94R4) or a nitrogen atom,
G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,
G7 is C(xe2x80x94R7), an oxygen atom, a sulfur atom, or a nitrogen atom optionally substituted by R8,
xe2x80x83wherein R1, R2, R3 and R4 are each independently,
(1) hydrogen atom,
(2) C1-6 alkanoyl,
(3) carboxyl,
(4) cyano,
(5) nitro,
(6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,
group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,
(7) xe2x80x94COORa1 
xe2x80x83wherein Ra1 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B or glucuronic acid residue,
group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, xe2x80x94(CH2)rxe2x80x94COORb1, xe2x80x94(CH2)rxe2x80x94CONRb1Rb2, (CH2)rxe2x80x94NRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1xe2x80x94CORb2, xe2x80x94(CH2)rxe2x80x94NHSO2Rb1, xe2x80x94(CH2)rxe2x80x94ORb1, xe2x80x94(CH2)rxe2x80x94SRb1, xe2x80x94(CH2)rxe2x80x94SO2Rb1 and xe2x80x94(CH2)rxe2x80x94SO2NRb1Rb2 
xe2x80x83wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,
(8) xe2x80x94CONRa2Ra3 
xe2x80x83wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),
(9) xe2x80x94C (xe2x95x90NRa4)NH2 
xe2x80x83wherein Ra4 is hydrogen atom or hydroxyl group,
(10) xe2x80x94NHRa5 
xe2x80x83wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,
(11) xe2x80x94ORa6 
xe2x80x83wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),
(12) xe2x80x94SO2Ra7 
xe2x80x83wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,
(13) xe2x80x94P(xe2x95x90O) (ORa31)2 
xe2x80x83wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B
or
(14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and
xe2x80x83R7 and R8 are each hydrogen atom or optionally substituted C1-6 alkyl (as defined above),
ring Cy is
(1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy,
(2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or
(3) 
xe2x80x83wherein u and v are each independently an integer of 1 to 3,
ring A is
(1) C6-14 aryl,
(2) C3-8 cycloalkyl,
(3) C3-8 cycloalkenyl or
(4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
R5 and R6 are each independently
(1) hydrogen atom,
(2) halogen atom,
(3) optionally substituted C1-6 alkyl (as defined above)
or
(4) xe2x80x94ORa8 
xe2x80x83wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and
X is
(1) hydrogen atom,
(2) halogen atom,
(3) cyano,
(4) nitro,
(5) amino, C1-6 alkanoylamino,
(6) C1-6 alkylsulfonyl,
(7) optionally substituted C1-6 alkyl (as defined above),
(8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,
(9) xe2x80x94COORa9 
xe2x80x83wherein Ra9 is hydrogen atom or C1-6 alkyl,
(10) xe2x80x94CONHxe2x80x94(CH2)1xe2x80x94Ra10 
xe2x80x83wherein Ra10 is optionally substituted C1-6 alkyl (as defined above), C1-6 alkoxycarbonyl or C1-6 alkanoylamino and 1 is 0 or an integer of 1 to 6,
(11) xe2x80x94ORa11 
xe2x80x83wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above)
or
(12) 
xe2x80x83wherein
ring B is
(1xe2x80x2) C6-14 aryl,
(2xe2x80x2) C3-8 cycloalkyl or
(3xe2x80x2) heterocyclic group (as defined above),
each Z is independently
(1xe2x80x2) a group selected from the following group D,
(2xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(3xe2x80x2) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(4xe2x80x2) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(5xe2x80x2) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D,
xe2x80x83wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or
(6xe2x80x2) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
xe2x80x83wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, as defined above,
group D:
(a) hydrogen atom,
(b) halogen atom,
(c) cyano,
(d) nitro,
(e) optionally substituted C1-6 alkyl (as defined above),
(f) xe2x80x94(CH2)txe2x80x94CORa18,
xe2x80x83(hereinafter each t means independently 0 or an integer of 1 to 6),
wherein Ra18 is
(1xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(2xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or
(3xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B
xe2x80x83wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
(g) xe2x80x94(CH2)txe2x80x94COORa19 
xe2x80x83wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(h) xe2x80x94(CH2)txe2x80x94CONRa27Ra28 
xe2x80x83wherein Ra27 and Ra28 are each independently,
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
xe2x80x83wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,
(7xe2x80x3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(8xe2x80x3) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(9xe2x80x3) hydroxyl group or
(10xe2x80x3) C1-6 alkoxy,
(i) xe2x80x94(CH2)txe2x80x94C (xe2x95x90NRa33)NH2 
xe2x80x83wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy, p3 (j) xe2x80x94(CH2)txe2x80x94ORa20 
xe2x80x83wherein Ra20 is
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) optionally substituted C2-6 alkenyl (as defined above),
(4xe2x80x3) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,
(5xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(7xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(8xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(9xe2x80x3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or
(10xe2x80x3) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(k) xe2x80x94(CH2)txe2x80x94Oxe2x80x94(CH2)pxe2x80x94CORa21 
xe2x80x83wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
xe2x80x83and p is 0 or an integer of 1 to 6,
(l) xe2x80x94(CH2)txe2x80x94NRa22Ra23 
wherein Ra22 and Ra23 are each independently
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or
(6xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(m) xe2x80x94(CH2)txe2x80x94NRa29COxe2x80x94Ra24 
xe2x80x83wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and
xe2x80x83Ra24 is
(1xe2x80x3) amino,
(2xe2x80x3) C1-6 alkylamino,
(3xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(4xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B or
(6xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
xe2x80x83(n) xe2x80x94(CH2)txe2x80x94NRa29SO2xe2x80x94Ra25 
xe2x80x83wherein Ra29 is as defined above, and Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(o) xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 
xe2x80x83wherein Ra25 is as defined above, and q is 0, 1 or 2,
(p) xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26 
xe2x80x83wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
and
(q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and
w is an integer of 1 to 3, and
Y is
(1xe2x80x2) a single bond,
(2xe2x80x2) C1-6 alkylene,
(3xe2x80x2) C2-6 alkenylene,
(4xe2x80x2) xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94,
xe2x80x83(hereinafter m and n are each independently 0 or an integer of 1 to 6),
(5xe2x80x2) xe2x80x94COxe2x80x94,
(6xe2x80x2) xe2x80x94CO2xe2x80x94(CH2)nxe2x80x94,
(7xe2x80x2) xe2x80x94CONHxe2x80x94(CH2)nxe2x80x94NHxe2x80x94,
(8xe2x80x2) xe2x80x94NHCO2xe2x80x94,
(9xe2x80x2) xe2x80x94NHCONHxe2x80x94,
(10xe2x80x2) xe2x80x94Oxe2x80x94(CH2)nxe2x80x94COxe2x80x94,
(11xe2x80x2) xe2x80x94Oxe2x80x94(CH2)nxe2x80x94Oxe2x80x94,
(12xe2x80x2) xe2x80x94SO2xe2x80x94,
(13xe2x80x2) xe2x80x94(CH2)mxe2x80x94NRa12xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra12 is
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x3) xe2x80x94CORb5 
xe2x80x83wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x3) xe2x80x94COORb5 (Rb5 is as defined above) or
(7xe2x80x3) xe2x80x94SO2Rb5 (Rb5 is as defined above),
(14xe2x80x2) xe2x80x94NRa12COxe2x80x94 (Ra12 is as defined above),
(15xe2x80x2) xe2x80x94CONRa13xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(16xe2x80x2) xe2x80x94CONHxe2x80x94CHRa14xe2x80x94
xe2x80x83wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(17xe2x80x2) xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra15 and Ra16 are each independently
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) carboxyl,
(3xe2x80x3) C1-6 alkyl,
(4xe2x80x3) xe2x80x94ORb6 
xe2x80x83wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or
(5xe2x80x3) xe2x80x94NHRb7 
xe2x80x83wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally
(6xe2x80x3) 
xe2x80x83wherein nxe2x80x2, ring Bxe2x80x2, Zxe2x80x2 and wxe2x80x2 are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,
(18xe2x80x2) xe2x80x94(CH2)nxe2x80x94NRa12xe2x80x94CHRa15xe2x80x94 (Ra12 and Ra15 are each as defined above),
(19xe2x80x2) xe2x80x94NRa17SO2xe2x80x94
xe2x80x83wherein Ra17 is hydrogen atom or C1-6 alkyl,
(20xe2x80x2) xe2x80x94S(O)exe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above),
or
(21xe2x80x2) xe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 (Ra15 and Ra16 are each as defined above).
(2) The therapeutic agent of (1) above, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is (are) a nitrogen atom.
(3) The therapeutic agent of (2) above, wherein G2 is C(xe2x80x94R2) and G6 is a carbon atom.
(4) The therapeutic agent of (2) or (3) above, wherein G5 is a nitrogen atom.
(5) The therapeutic agent of (1) above, wherein, in formula [I], the moiety 
is a fused ring selected from 
(6) The therapeutic agent of (5) above, wherein, in formula [I], the moiety 
is a fused ring selected from 
(7) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-1]
wherein each symbol is as defined in (1), or a pharmaceutically acceptable salt thereof as an active ingredient.
(8) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-2]
wherein each symbol is as defined in (1), or a pharmaceutically acceptable salt thereof as an active ingredient.
(9) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-3]
wherein each symbol is as defined in (1), or a pharmaceutically acceptable salt thereof as an active ingredient.
(10) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-4]
wherein each symbol is as defined in (1), or a pharmaceutically acceptable salt thereof as an active ingredient.
(11) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, xe2x80x94COORa1, xe2x80x94CONRa2Ra3, xe2x80x94SO2Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (1)), 
(12) The therapeutic agent of (11) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, xe2x80x94COORa1, xe2x80x94CONRa2Ra3 or xe2x80x94SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (1).
(13) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is xe2x80x94COORa1 wherein Ra1 is glucuronic acid residue.
(14) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.
(15) The therapeutic agent of any of (1) to (14) above, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino.
(16) The therapeutic agent of any of (1) to (14) above, wherein the ring Cy is 
wherein each symbol is as defined in (1).
(17) The therapeutic agent of any of (1) to (16) above, wherein the ring A is C6-14 aryl.
(18) The therapeutic agent of any of (1) to (17) above, wherein at least one substituent optionally substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy.
(19) The therapeutic agent of any of (1) to (17) above, wherein the Y is xe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 wherein each symbol is as defined in (1).
(20) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D.
(21) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by Z is a heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups: 
wherein E1 is an oxygen atom, a sulfur atom or N(xe2x80x94Ra35) E2 is an oxygen atom, CH2 or N(xe2x80x94Ra35), E3 is an oxygen atom or a sulfur atom, wherein each Ra35 is independently hydrogen atom or C1-E alkyl, f is an integer of 1 to 3, and h and hxe2x80x2 are the same or different and each is an integer of 1 to 3.
(22) The therapeutic agent of (21) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D wherein said heterocyclic group is selected from the following groups: 
wherein each symbol is as defined in (21).
(23) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94CONRa27Ra28 wherein each symbol is as defined in (1), and at least one of Ra27 and Ra28 is C1-6 alkoxy.
(24) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94C(xe2x95x90NRa33)NH2 wherein each symbol is as defined in (1), and Ra33 is hydroxyl group or C1-6 alkoxy.
(25) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94Oxe2x80x94(CH2)pxe2x80x94CORa21 wherein each symbol is as defined in (1), and Ra21 is amino.
(26) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94NRa29COxe2x80x94Ra24 wherein each symbol is as defined in (1), and Ra24 is amino or C1-6 alkylamino.
(27) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94NRa22Ra23 wherein each symbol is as defined in (1), and at lease one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B.
(28) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.
(29) The therapeutic agent of (1) above, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient: 
wherein
a broken line is a single bond or a double bond,
G1 is C(xe2x80x94R1) or a nitrogen atom,
G2 is C(xe2x80x94R2) or a nitrogen atom,
G3 is C(xe2x80x94R3) or a nitrogen atom,
G4 is C(xe2x80x94R4) or a nitrogen atom,
G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,
G7 is C(xe2x80x94R7), an oxygen atom, a sulfur atom, or a nitrogen atom optionally substituted by R8,
xe2x80x83wherein R1, R2, R3 and R4 are each independently,
(1) hydrogen atom,
(2) C1-6 alkanoyl,
(3) carboxyl,
(4) cyano,
(5) nitro,
(6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,
group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxycarbonyl and (C1-6 alkylamino,
(7) xe2x80x94COORa1 
xe2x80x83wherein Ra1 is optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B,
group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, xe2x80x94(CH2)rxe2x80x94COORb, xe2x80x94(CH2)rxe2x80x94CONRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1xe2x80x94CORb2, xe2x80x94(CH2)rxe2x80x94NHSO2Rb1, xe2x80x94(CH2)rxe2x80x94ORb1, xe2x80x94(CH2)rxe2x80x94SRb1, xe2x80x94(CH2)rxe2x80x94SO2Rb1 and xe2x80x94(CH2)rxe2x80x94SO2NRb1Rb2 
xe2x80x83wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,
(8) xe2x80x94CONRa2Ra3 
xe2x80x83wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),
(9) xe2x80x94C (xe2x95x90NRa4)NH2 
xe2x80x83wherein Ra4 is hydrogen atom or hydroxyl group,
(10) xe2x80x94NHRa5 
xe2x80x83wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,
(11) xe2x80x94ORa6 
xe2x80x83wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl(as defined above),
(12) xe2x80x94SO2Ra7 
xe2x80x83wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino
or
(13) xe2x80x94P(xe2x95x90O) (ORa31)2 
xe2x80x83wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, and
xe2x80x83R7 and R8 are each hydrogen atom or optionally substituted C1-6 alkyl(as defined above),
ring Cy is
(1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy,
(2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or
(3) 
xe2x80x83wherein u and v are each independently an integer of 1 to 3,
ring A is
(1) C6-14 aryl,
(2) C3-8 cycloalkyl,
(3) C3-8 cycloalkenyl or
(4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
R5 and R6 are each independently
(1) hydrogen atom,
(2) halogen atom,
(3) optionally substituted C1-6 alkyl (as defined above)
or
(4) xe2x80x94ORa8 
xe2x80x83wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and
X is
(1) hydrogen atom,
(2) halogen atom,
(3) cyano,
(4) nitro,
(5) amino, C1-6 alkanoylamino,
(6) C1-6 alkylsulfonyl,
(7) optionally substituted C1-6 alkyl (as defined above),
(8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,
(9) xe2x80x94COORa9 wherein Ra9 is hydrogen atom or C1-6 alkyl,
(10) xe2x80x94CONHxe2x80x94(CH2)lxe2x80x94Ra10 
xe2x80x83wherein Ra10 is optionally substituted C1-6 alkyl (as defined above), C1-6 alkoxycarbonyl or C1-6 alkanoylamino and 1 is 0 or an integer of 1 to 6,
(11) xe2x80x94ORa11 
xe2x80x83wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above)
or
(12) 
xe2x80x83wherein
ring B is
(1xe2x80x2) C6-14 aryl,
(2xe2x80x2) C3-8 cycloalkyl or
(3xe2x80x2) heterocyclic group (as defined above),
each Z is independently
(1xe2x80x2) a group selected from the following group D,
(2xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(3xe2x80x2) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(4xe2x80x2) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D or
(5xe2x80x2) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D
xe2x80x83wherein the heterocyclic group has 1 to 4; heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
group D:
(a) hydrogen atom,
(b) halogen atom,
(c) cyano,
(d) nitro,
(e) optionally substituted C1-6 alkyl (as defined above),
(f) xe2x80x94(CH2)txe2x80x94CORa18,
xe2x80x83(hereinafter each t means independently 0 or an integer of 1 to 6),
wherein Ra18 is
(1xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(2xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or
(3xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
(g) xe2x80x94(CH2)txe2x80x94COORa19 
wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(h) xe2x80x94(CH2)txe2x80x94CONRa27Ra28 
wherein Ra27 and Ra28 are each independently,
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
xe2x80x83wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,
(7xe2x80x3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or
(8xe2x80x3) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(i) xe2x80x94(CH2)txe2x80x94C(xe2x95x90NRa33)NH2 
xe2x80x83wherein Ra33 is hydrogen atom or C1-6 alkyl,
(j) xe2x80x94(CH2)txe2x80x94ORa20 
xe2x80x83wherein Ra20 is
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) optionally substituted C2-6 alkenyl (as defined above),
(4xe2x80x3) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,
(5xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(7xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(8xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(9xe2x80x3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or
(10xe2x80x3) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(k) xe2x80x94(CH2)txe2x80x94Oxe2x80x94(CH2)pxe2x80x94CORa21 
xe2x80x83wherein Ra21 is C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,
(l) xe2x80x94(CH2)txe2x80x94NRa22Ra23 
xe2x80x83wherein Ra22 and Ra23 are each independently
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or
(5xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(m) xe2x80x94(CH2)txe2x80x94NRa29COxe2x80x94Ra24 
xe2x80x83wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, Ra24 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(n) xe2x80x94(CH2)txe2x80x94NHSO2xe2x80x94Ra25 
xe2x80x83wherein Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(o) xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 
xe2x80x83wherein Ra25 is as defined above, and q is 0, 1 or 2,
and
(p) xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26 
xe2x80x83wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by(1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
w is an integer of 1 to 3, and
Y is
(1xe2x80x2) a single bond,
(2xe2x80x2) C1-6 alkylene,
(3xe2x80x2) C2-6 alkenylene,
(4xe2x80x2) xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94,
xe2x80x83(hereinafter m and n are each independently 0 or an integer of 1 to 6),
(5xe2x80x2) xe2x80x94COxe2x80x94,
(6xe2x80x2) xe2x80x94CO2xe2x80x94(CH2)nxe2x80x94,
(7xe2x80x2) xe2x80x94CONHxe2x80x94(CH2)nxe2x80x94NHxe2x80x94,
(8xe2x80x2) xe2x80x94NHCO2xe2x80x94,
(9xe2x80x2) xe2x80x94NHCONHxe2x80x94,
(10xe2x80x2) xe2x80x94Oxe2x80x94(CH2)nxe2x80x94COxe2x80x94,
(11xe2x80x2) xe2x80x94Oxe2x80x94(CH2)nxe2x80x94Oxe2x80x94,
(12xe2x80x2) xe2x80x94SO2xe2x80x94,
(13xe2x80x2) xe2x80x94(CH2)mNRa12xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra12 is
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x3) xe2x80x94CORb5 
xe2x80x83wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x3) xe2x80x94COORb5 (Rb5 is as defined above) or
(7xe2x80x3) xe2x80x94SO2Rb5 (Rb5 is as defined above),
(14xe2x80x2) xe2x80x94NRa12COxe2x80x94 (Ra12 is as defined above),
(15xe2x80x2) xe2x80x94CONRa13xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(16xe2x80x2) xe2x80x94CONHxe2x80x94CHRa14xe2x80x94
xe2x80x83wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(17xe2x80x2) xe2x80x94Oxe2x80x94(CH)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra15 and Ra16 are each independently
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) carboxyl,
(3xe2x80x3) C1-6 alkyl,
(4xe2x80x3) xe2x80x94ORb6 
xe2x80x83wherein Rb6 is C1-6 alkyl or C6-14 alkyl C1-6 alkyl, or
(5xe2x80x3) xe2x80x94NHRb7 
xe2x80x83wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally
(6xe2x80x3) 
xe2x80x83wherein nxe2x80x2, ring Bxe2x80x2, Zxe2x80x2 and wxe2x80x2 are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,
(18xe2x80x2) xe2x80x94(CH2)nxe2x80x94NRa12xe2x80x94CHRa15xe2x80x94 (Ra12 and Ra15 are each as defined above),
(19xe2x80x2) xe2x80x94NRa17SO2xe2x80x94
xe2x80x83wherein Ra17 is hydrogen atom or C1-6 alkyl
or
(20xe2x80x2) xe2x80x94S(O)exe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above).
(30) The therapeutic agent of (29) above, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is (are) a nitrogen atom.
(31) The therapeutic agent of (30) above, wherein G2 is C(xe2x80x94R2) and G6 is a carbon atom.
(32) The therapeutic agent of (30) or (31) above, wherein G5 is a nitrogen atom.
(33) The therapeutic agent of (29) above, wherein, in formula [I], the moiety 
is a fused ring selected from 
(34) The therapeutic agent of (33) above, wherein, in formula [I], the moiety 
is a fused ring selected from 
(35) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-1]
wherein each symbol is as defined in (29),
or a pharmaceutically acceptable salt thereof as an active ingredient.
(36) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-2]
wherein each symbol is as defined in (29),
or a pharmaceutically acceptable salt thereof as an active ingredient.
(37) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-3]
wherein each symbol is as defined in (29),
or a pharmaceutically acceptable salt thereof as an active ingredient.
(38) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-4]
wherein each symbol is as defined in (29),
or a pharmaceutically acceptable salt thereof as an active ingredient.
(39) The therapeutic agent of any of (29) to (38) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, xe2x80x94COORa1, xe2x80x94CONRa2Ra3 or xe2x80x94SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (29).
(40) The therapeutic agent of any of (29) to (39) above, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl.
(41) The therapeutic agent of any of (29) to (40) above, wherein the ring A is C6-14 aryl.
(42) A fused ring compound of the following formula [II]
wherein
the moiety 
xe2x80x83is a fused ring selected from 
xe2x80x83wherein R1, R2, R3 and R4 are each independently,
(1) hydrogen atom,
(2) C1-6 alkanoyl,
(3) carboxyl,
(4) cyano,
(5) nitro,
(6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,
group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,
(7) xe2x80x94COORa1 
xe2x80x83wherein Ra1 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B or glucuronic acid residue,
group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, xe2x80x94(CH2)rxe2x80x94COORb1, xe2x80x94(CH2)rxe2x80x94CONRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1xe2x80x94COb2, xe2x80x94(CH2)rxe2x80x94NHSO2Rb1, xe2x80x94(CH2)rxe2x80x94ORb1, xe2x80x94(CH2)rxe2x80x94SRb1, xe2x80x94(CH2)rxe2x80x94SO2Rb1 and xe2x80x94(CH2)rxe2x80x94SO2NRb1Rb2 
xe2x80x83wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,
(8) xe2x80x94CONRa2Ra3 
xe2x80x83wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),
(9) xe2x80x94C(xe2x95x90NRa4)NH2 
xe2x80x83wherein Ra4 is hydrogen atom or hydroxyl group,
(10) xe2x80x94NHRa5 
xe2x80x83wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,
(11) xe2x80x94ORa6 
xe2x80x83wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),
(12) xe2x80x94SO2Ra7 
xe2x80x83wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,
(13) xe2x80x94P(xe2x95x90O) (ORa31)2 
xe2x80x83wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
or
(14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and
R7 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),
ring Cyxe2x80x2 is
(1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy, or
(2) 
xe2x80x83wherein u and v are each independently an integer of 1 to 3,
ring Axe2x80x2 is a group selected from a group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,
R5xe2x80x2 and R6xe2x80x2 are each independently
(1) hydrogen atom,
(2) halogen atom,
(3) optionally substituted C1-6 alkyl (as defined above)
or
(4) hydroxyl group
ring B is
(1) C6-14 aryl,
(2) C3-8 cycloalkyl or
(3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
each Z is independently
(1) a group selected from the following group D
(2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(5) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D
xe2x80x83wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or
(6) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D
xe2x80x83wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, as defined above, group D:
(a) hydrogen atom,
(b) halogen atom,
(c) cyano,
(d) nitro,
(e) optionally substituted C1-6 alkyl (as defined above),
(f) xe2x80x94(CH2)txe2x80x94CORa18,
xe2x80x83(hereinafter each t means independently 0 or an integer of 1 to 6),
xe2x80x83wherein Ra18 is
(1xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(2xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or
(3xe2x80x2) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
(g) xe2x80x94(CH2)txe2x80x94COORa19 
xe2x80x83wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(h) xe2x80x94(CH2)txe2x80x94CONRa27Ra28 
xe2x80x83wherein Ra27 and Ra28 are each independently,
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
xe2x80x83wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,
(7xe2x80x3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(8xe2x80x3) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(9xe2x80x3) hydroxyl group or
(10xe2x80x3) C1-6 alkoxy,
(i) (CH2)txe2x80x94C(xe2x95x90NRa33)NH2 
xe2x80x83wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,
(j) xe2x80x94(CH2)txe2x80x94ORa20 
xe2x80x83wherein Ra20 is
(1xe2x80x2) hydrogen atom,
(2xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x2) optionally substituted C2-6 alkenyl (as defined above),
(4xe2x80x2) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,
(5xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x2) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(7xe2x80x2) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(8xe2x80x2) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(9xe2x80x2) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or
(10xe2x80x2) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(k) xe2x80x94(CH2)txe2x80x94Oxe2x80x94(CH2)pxe2x80x94CORa21 
xe2x80x83wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
xe2x80x83and p is 0 or an integer of 1 to 6,
(l) xe2x80x94(CH2)txe2x80x94NRa22Ra23 
xe2x80x83wherein Ra22 and Ra23 are each independently
(1xe2x80x2) hydrogen atom,
(2xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x2) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x2) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group, B or
(6xe2x80x2) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(m) xe2x80x94(CH2)txe2x80x94NRa29COxe2x80x94Ra24 
xe2x80x83wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and
xe2x80x83Ra24 is
(1xe2x80x2) amino,
(2xe2x80x2) C1-6 alkylamino,
(3xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(4xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x2) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, or
(6xe2x80x2) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(n) xe2x80x94(CH2)txe2x80x94NRa29SO2xe2x80x94Ra25 
xe2x80x83wherein Ra29 is as defined above, and Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(o) xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 
xe2x80x83wherein Ra25 is as defined above, and q is 0, 1 or 2,
(p) xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26 
xe2x80x83wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B
xe2x80x83or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
and
(q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
w is an integer of 1 to 3, and
Y is
(1) a single bond,
(2) C1-6 alkylene,
(3) C2-6 alkenylene,
(4) xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94,
xe2x80x83(hereinafter m and n are each independently 0 or an integer of 1 to 6),
(5) xe2x80x94COxe2x80x94,
(6) xe2x80x94CO2xe2x80x94(CH2)nxe2x80x94,
(7) xe2x80x94CONHxe2x80x94(CH2)nxe2x80x94NHxe2x80x94,
(8) xe2x80x94NHCO2xe2x80x94,
(9) xe2x80x94NHCONHxe2x80x94,
(10) xe2x80x94Oxe2x80x94(CH2)nxe2x80x94COxe2x80x94,
(11) xe2x80x94Oxe2x80x94(CH2)nxe2x80x94Oxe2x80x94,
(12) xe2x80x94SO2xe2x80x94,
(13) xe2x80x94(CH2)mNRa12xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra12 is
(1xe2x80x2) hydrogen atom,
(2xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x2) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5) xe2x80x94CORb5 
xe2x80x83wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x2) xe2x80x94COORb5 (Rb5 is as defined above) or
(7xe2x80x2) xe2x80x94SO2Rb5 (Rb5 is as defined above),
(14) xe2x80x94NRa12COxe2x80x94 (Ra12 is as defined above),
(15) xe2x80x94CONRa13xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(16) xe2x80x94CONHxe2x80x94CHRa14xe2x80x94
xe2x80x83wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(17) xe2x80x94Oxe2x80x94(CH2)mCRa15Ra16xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra15 and Ra16 are each independently
(1xe2x80x2) hydrogen atom,
(2xe2x80x2) carboxyl,
(3xe2x80x2) C1-6 alkyl,
(4xe2x80x2) xe2x80x94ORb6 
xe2x80x83wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or
(5xe2x80x2) xe2x80x94NHRb7 
xe2x80x83wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or
xe2x80x83Ra15 is optionally
(6xe2x80x2) 
xe2x80x83wherein nxe2x80x2, ring Bxe2x80x2, Zxe2x80x2 and wxe2x80x2 are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,
(18) xe2x80x94(CH2)nxe2x80x94NRa12xe2x80x94CHRa15xe2x80x94(Ra12 and Ra15 are each as defined above),
(19) xe2x80x94NRa17SO2xe2x80x94wherein Ra17 is hydrogen atom or C1-6 alkyl,
(20) xe2x80x94S(O)exe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above),
or
(21) xe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)xe2x80x94(Ra15 and Ra16 are each as defined above),
or a pharmaceutically acceptable salt thereof.
(43) The fused ring compound of (42) above, which is represented by the following formula [II-1]
wherein each symbol is as defined in (42),
or a pharmaceutically acceptable salt thereof.
(44) The fused ring compound of (42) above, which is represented by the following formula [II-2]
wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.
(45) The fused ring compound of (42) above, which is represented by the following formula [II-3]
wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.
(46) The fused ring compound of (42) above, which is represented by the following formula [II-4]
wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.
(47) The fused ring compound of any of (42) to (46) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, xe2x80x94COORa1, xe2x80x94CONRa2Ra3, xe2x80x94SO2Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (42)), 
or a pharmaceutically acceptable salt thereof.
(48) The fused ring compound of (47) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, xe2x80x94COORa1 or xe2x80x94SO2Ra7 wherein Ra1 and Ra7 are as defined in (42), or a pharmaceutically acceptable salt thereof.
(49) The fused ring compound of (48) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or xe2x80x94COORa1 wherein Ra1 is as defined in (42), or a pharmaceutically acceptable salt thereof.
(50) The fused ring compound of (49) above, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.
(51) The fused ring compound of any of (42) to (46) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or xe2x80x94COORa1 wherein Ra1 is glucuronic acid residue, or a pharmaceutically acceptable salt thereof.
(52) The fused ring compound of any of (42) to (46) above, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.
(53) The fused ring compound of any of (42) to (52) above, wherein the ring Cyxe2x80x2 is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.
(54) The fused ring compound of (42) above, wherein the ring Cyxe2x80x2 is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.
(55) The fused ring compound of any of (42) to (52) above, wherein the ring Cyxe2x80x2 is 
wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.
(56) The fused ring compound of any of (42) to (55) above, wherein the ring Axe2x80x2 is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.
(57) The fused ring compound of (56) above, wherein the(ring Axe2x80x2 is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.
(58) The fused ring compound of (57) above, wherein the ring Axe2x80x2 is phenyl, or a pharmaceutically acceptable salt thereof.
(59) The fused ring compound of any of (42) to (58) above, wherein at least one substituent optionaly substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.
(60) The fused ring compound of any of (42) to (59) above, wherein the Y is xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94, xe2x80x94NHCO2xe2x80x94, xe2x80x94CONHxe2x80x94CHRa14xe2x80x94, xe2x80x94(CH2)mxe2x80x94NRa12xe2x80x94(CH2)nxe2x80x94, xe2x80x94CONRa13xe2x80x94(CH2)n, xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 or xe2x80x94(CH2)nxe2x80x94NRa12xe2x80x94CHRa15xe2x80x94 (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.
(61) The fused ring compound of (42) above, wherein the Y is xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94 or xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.
(62) The fused ring compound of (61) above, wherein the Y is xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94 wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.
(63) The fused ring compound of any of (42) to (59) above, wherein the Y is xe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.
(64) The fused ring compound of any of (42) to (63) above, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cyxe2x80x2 is cyclopentyl, cyclohexyl or cycloheptyl, and the ring Axe2x80x2 is phenyl, or a pharmaceutically acceptable salt thereof.
(65) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D, or a pharmaceutically acceptable salt thereof.
(66) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups: 
wherein E1 is an oxygen atom, a sulfur atom or N(xe2x80x94Ra35), E2 is an oxygen atom, CH2 or N(xe2x80x94Ra35), E3 is an oxygen atom or a sulfur atom, wherein each Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and hxe2x80x2 are the same or different and each is an integer of 1 to 3, or a pharmaceutically acceptable salt thereof.
(67) The fused ring compound of (66) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups: 
wherein each symbol is as defined in (66), or a pharmaceutically acceptable salt thereof.
(68) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94CONRa27Ra28 wherein each symbol is as defined in (42), and at least one of Ra27 and Ra28 is C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.
(69) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94C(xe2x95x90NRa33)NH2 wherein each symbol is as defined in (42), and Ra33 is hydroxyl group or C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.
(70) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94Oxe2x80x94(CH2)pxe2x80x94CORa21 wherein each symbol is as defined in (42), and Ra21 is amino, or a pharmaceutically acceptable salt thereof.
(71) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94NRa29COxe2x80x94Ra24 wherein each symbol is as defined in (42), and Ra24 is amino or C1-6 alkylamino, or a pharmaceutically acceptable salt thereof.
(72) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is xe2x80x94(CH2)txe2x80x94NRa22Ra23 wherein each symbol is as defined in (42), and at least one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B, or a pharmaceutically acceptable salt thereof.
(73) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.
(74) The fused ring compound of (42) above, which is represented by the following formula [II]
wherein
the moiety 
xe2x80x83is a fused ring selected from 
wherein R1, R2, R3 and R4 are each independently,
(1) hydrogen atom,
(2) C1-6 alkanoyl,
(3) carboxyl,
(4) cyano,
(5) nitro,
(6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,
group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,
(7) xe2x80x94COORa1 
xe2x80x83wherein Ra1 is optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B,
group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, xe2x80x94(CH2)rxe2x80x94COORb1, xe2x80x94(CH2)rxe2x80x94CONRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1Rb2, xe2x80x94(CH2)rNRb1xe2x80x94CORb2, xe2x80x94(CH2)rxe2x80x94NHSO2Rb1, (CH2)rxe2x80x94ORb1, xe2x80x94(CH2)rxe2x80x94SRb1, xe2x80x94(CH2)rxe2x80x94SO2Rb1 and xe2x80x94(CH2)rxe2x80x94SO2NRb1Rb2 
xe2x80x83wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,
(8) xe2x80x94CONRa2Ra3 
xe2x80x83wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),
(9) xe2x80x94C(xe2x95x90NRa4)NH2 
xe2x80x83wherein Ra4 is hydrogen atom or hydroxyl group,
(10) xe2x80x94NHRa5 
xe2x80x83wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,
(11) xe2x80x94ORa6 
xe2x80x83wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),
(12) xe2x80x94SO2Ra7 
xe2x80x83wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino
or
(13) xe2x80x94P(xe2x95x90O) (ORa31)2 
xe2x80x83wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, and
R7 is hydrogen atom or optionally substituted
C1-6 alkyl (as defined above),
ring Cyxe2x80x2 is
(1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy, or
(2) 
xe2x80x83wherein u and v are each independently an integer of 1 to 3,
ring Axe2x80x2 is a group selected from a group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,
R5xe2x80x2 and R6xe2x80x2 are each independently
(1) hydrogen atom,
(2) halogen atom,
(3) optionally substituted C1-6 alkyl (as defined above) or
(4) hydroxyl group
ring B is
(1) C6-14 aryl,
(2) C3-8 cycloalkyl or
(3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
each Z is independently
(1) a group selected from the following group D,
(2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,
(3) C3-8 cycloalkyl optionally substituted by 1to 5 substituent(s) selected from the following group D,
(4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D or
(5) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
group D:
(a) hydrogen atom,
(b) halogen atom,
(c) cyano,
(d) nitro,
(e) optionally substituted C1-6 alkyl (as defined above),
(f) xe2x80x94(CH2)txe2x80x94CORa18,
xe2x80x83(hereinafter each t means independently 0 or an integer of 1 to 6),
xe2x80x83wherein Ra18 is
(1xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(2xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or
(3xe2x80x2) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B
xe2x80x83wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,
(g) xe2x80x94(CH2)txe2x80x94COORa19 
xe2x80x83wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(h) xe2x80x94(CH2)txe2x80x94CONRa27Ra28 
xe2x80x83wherein Ra27 and Ra28 are each independently,
(1xe2x80x3) hydrogen atom,
(2xe2x80x3) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x3) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x3) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x3) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x3) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
xe2x80x83wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,
(7xe2x80x3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or
(8xe2x80x3) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(i) xe2x80x94(CH2)txe2x80x94C(xe2x95x90NRa33)NH2 
xe2x80x83wherein Ra33 is hydrogen atom or C1-6 alkyl,
(j) xe2x80x94(CH2)txe2x80x94ORa20 
xe2x80x83wherein Ra20 is
(1xe2x80x2) hydrogen atom,
(2xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x2) optionally substituted C2-6 alkenyl (as defined above),
(4xe2x80x2) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,
(5xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x2) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(7xe2x80x2) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(8xe2x80x2) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(9xe2x80x2) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or
(10xe2x80x2) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(k) xe2x80x94(CH2)txe2x80x94Oxe2x80x94(CH2)pxe2x80x94CORa21 
xe2x80x83wherein Ra21 is C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,
(l) xe2x80x94(CH2)txe2x80x94NRa22Ra23 
xe2x80x83wherein Ra22 and R23 are each independently
(1xe2x80x2) hydrogen atom,
(2xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x2) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or
(5xe2x80x2) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(m) xe2x80x94(CH2)txe2x80x94NRa29CORa24 
xe2x80x83wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, Ra24 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(n) xe2x80x94(CH2)txe2x80x94NHSO2xe2x80x94Ra25 
xe2x80x83wherein Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B
xe2x80x83or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(o) xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 
xe2x80x83wherein Ra25 is as defined above, and q is 0, 1 or 2,
and
(p) xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26 
xe2x80x83wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,
w is an integer of 1 to 3, and
Y is
(1) a single bond,
(2) C1-6 alkylene,
(3) C2-6 alkenylene,
(4) xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94,
xe2x80x83(hereinafter m and n are each independently 0 or an integer of 1 to 6),
(5) xe2x80x94COxe2x80x94,
(6) xe2x80x94CO2xe2x80x94(CH2)nxe2x80x94,
(7) xe2x80x94CONHxe2x80x94(CH2)nxe2x80x94NHxe2x80x94,
(8) xe2x80x94NHCO2xe2x80x94,
(9) xe2x80x94NHCONHxe2x80x94,
(10) xe2x80x94Oxe2x80x94(CH2)nxe2x80x94COxe2x80x94,
(11) xe2x80x94Oxe2x80x94(CH2)nxe2x80x94Oxe2x80x94,
(12) xe2x80x94SO2xe2x80x94,
(13) xe2x80x94(CH2)mNRa12xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra12 is
(1xe2x80x2) hydrogen atom,
(2xe2x80x2) optionally substituted C1-6 alkyl (as defined above),
(3xe2x80x2) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(4xe2x80x2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(5xe2x80x2) xe2x80x94CORb5 
xe2x80x83wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(6xe2x80x2) xe2x80x94COORb5 (Rb5 is as defined above) or
(7xe2x80x2) xe2x80x94SO2Rb5 (Rb5 is as defined above),
(14) xe2x80x94NR COxe2x80x94 (Ra12 is as defined above),
(15) xe2x80x94CONRa13xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(16) xe2x80x94CONHxe2x80x94CHRa14xe2x80x94
xe2x80x83wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,
(17) xe2x80x94Oxe2x80x94(CH2)mCRa15Ra16xe2x80x94(CH2)nxe2x80x94
xe2x80x83wherein Ra15 and Ra16 are each independently
(1xe2x80x2) hydrogen atom,
(2xe2x80x2) carboxyl,
(3xe2x80x2) C1-6 alkyl,
(4xe2x80x2) xe2x80x94ORb6 
xe2x80x83wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl,
or
(5xe2x80x2) xe2x80x94NHRb7 
xe2x80x83wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl,
xe2x80x83or Ra15 is optionally
(6xe2x80x2) 
xe2x80x83wherein nxe2x80x2, ring Bxe2x80x2, Zxe2x80x2 and wxe2x80x2 are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,
(18) xe2x80x94(CH2)nxe2x80x94NRa12xe2x80x94CHRa15xe2x80x94 (Ra12 and Ra15 each as defined above),
(19) xe2x80x94NRa17SO2xe2x80x94
xe2x80x83wherein Ra17 is hydrogen atom or C1-6 alkyl
or
(20) xe2x80x94S(O)exe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above)
or a pharmaceutically acceptable salt thereof.
(75) The fused ring compound of (74) above, which is represented by the following formula [II-1]
wherein each symbol is as defined in (74), or a pharmaceutically acceptable salt thereof.
(76) The fused ring compound of (74) above, which is represented by the following formula [II-2]
wherein each symbol is as defined in (74), or a pharmaceutically acceptable salt thereof.
(77) The fused ring compound of (74) above, which is represented by the following formula [II-3]
wherein each symbol is as defined in (74), or a pharmaceutically acceptable salt thereof.
(78) The fused ring compound of (74) above, which is represented by the following formula [II-4]
wherein each symbol is as defined in (74), or a pharmaceutically acceptable salt thereof.
(79) The fused ring compound of any of (74) to (78) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, xe2x80x94COORa1 or xe2x80x94SO2Ra7 wherein Ra1 and Ra7 are as defined in (74), or a pharmaceutically acceptable salt thereof.
(80) The fused ring compound of (79) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or xe2x80x94COORa1 wherein Ra1 is as defined in (74), or a pharmaceutically acceptable salt thereof.
(81) The fused ring compound of (80) above, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.
(82) The fused ring compound of any of (74) to (81) above, wherein the ring Cyxe2x80x2 is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.
(83) The fused ring compound of (82) above, wherein the ring Cyxe2x80x2 is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.
(84) The fused ring compound of any of (74) to (83) above, wherein the ring Axe2x80x2 is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.
(85) The fused ring compound of (84) above, wherein the ring Axe2x80x2 is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.
(86) The fused ring compound of (85) above, wherein the ring Axe2x80x2 is phenyl, or a pharmaceutically acceptable salt thereof.
(87) The fused ring compound of any of (74) to (86) above, wherein the Y is xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94, xe2x80x94NHCO2xe2x80x94, xe2x80x94CONHxe2x80x94CHRa14xe2x80x94, xe2x80x94(CH2)mxe2x80x94NRa12xe2x80x94(CH2)nxe2x80x94, xe2x80x94CONRa13xe2x80x94(CH2)nxe2x80x94, xe2x80x94Oxe2x80x94(CH2)mCRa15Ra16xe2x80x94(CH2)nxe2x80x94 or xe2x80x94(CH2)nxe2x80x94NRa12xe2x80x94CHRa15xe2x80x94 (wherein each symbol is as defined in (74)), or a pharmaceutically acceptable salt thereof.
(88) The fused ring compound of (87) above, wherein the Y is xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94 or xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 (wherein each symbol is as defined in (74)), or a pharmaceutically acceptable salt thereof.
(89) The fused ring compound of (88) above, wherein thus Y is xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94 wherein each symbol is as defined in (74), or a pharmaceutically acceptable salt thereof.
(90) The fused ring compound of any of (74) to (89) above, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cyxe2x80x2 is cyclopentyl, cyclohexyl or cycloheptyl, and the ring Axe2x80x2 is phenyl, or a pharmaceutically acceptable salt thereof.
(91) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of
ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 1),
2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 2),
ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (Example 3),
ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 4),
ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 5),
2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 6),
ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 7),
ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 8),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 9),
ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylate (Example 10),
1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylic acid (Example 11),
2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 12),
2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide (Example 13),
2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole (Example 14),
2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime (Example 15),
ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate (Example 16),
1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 17),
ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)benzimidazole-5-carboxylate (Example 18),
ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 19),
2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 20),
ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate (Example 21),
ethyl 2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 22),
ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 23),
2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 24),
ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 25),
2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 26),
ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 27),
ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate (Example 28),
ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylate (Example 29),
1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 30),
2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 31),
ethyl 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 32),
2-(4-benzyloxyphenyl)-1-cyclopentyl-N,N-dimethylbenzimidazole-5-carboxamide (Example 33),
2-(4-benzyloxyphenyl)-1-cyclopentyl-N-methoxy-N-methylbenzimidazole-5-carboxamide (Example 34),
2-(4-benzyloxyphenyl)-1-cyclopentyl-5-(1-hydroxy-1-methylethyl)benzimidazole (Example 35),
5-acetyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 36),
2-(4-benzyloxyphenyl)-1-cyclopentyl-N-(2-dimethylaminoethyl)-benzimidazole-5-carboxamide dihydrochloride (Example 37),
2-(4-benzyloxyphenyl)-1-cyclopentyl-5-nitrobenzimidazole (Example 38),
5-amino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole hydrochloride (Example 39),
5-acetylamino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 40),
2-(4-benzyloxyphenyl)-1-cyclopentyl-5-methanesulfonylaminobenzimidazole (Example 41),
5-sulfamoyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 42),
2-[4-(4-tert-butylbenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 43),
2-[4-(4-carboxybenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 44),
2-[4-(4-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 45),
2-{4-[(2-chloro-5-thienyl)methoxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 46),
1-cyclopentyl-2-[4-(4-trifluoromethylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid (Example 47),
1-cyclopentyl-2-[4-(4-methoxybenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 48),
1-cyclopentyl-2-[4-(4-pyridylmethoxy)phenyl]benzimidazole-5-carboxylic acid hydrochloride (Example 49),
1-cyclopentyl-2-[4-(4-methylbenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 50),
1-cyclopentyl-2-{4-[(3,5-dimethyl-4-isoxazolyl)methoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 51),
1-cyclopentyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylic acid (Example 52),
[2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazol-5-yl]-carbonylaminoacetic acid (Example 53),
2-[4-(2-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 54),
2-[4-(3-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 55),
2-(4-benzyloxyphenyl)-3-cyclopentylbenzimidazole-5-carboxylic acid (Example 56),
2-[4-(benzenesulfonylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 57),
1-cyclopentyl-2-[4-(3,5-dichlorophenylcarbonylamino)phenyl]-benzimidazole-5-carboxylic acid (Example 58),
2-{4-[(4-chlorophenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 59),
2-{4-[(4-tert-butylphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 60),
2-{4-[(4-benzyloxyphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 61),
trans-4-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]cyclohexan-1-ol (Example 62),
trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-methoxycyclohexane (Example 63),
2-(4-benzyloxyphenyl)-5-carboxymethyl-1-cyclopentylbenzimidazole (Example 64),
2-[1-benzyloxycarbonyl-4-piperidyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 65),
22-[(4-cyclohexylphenyl)carbonylamino]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 66), 5-carboxylic acid (Example 67),
1-cyclopentyl-2-[4-(3,4-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 68),
1-cyclopentyl-2-[4-(phenylcarbamoylamino)phenyl]benzimidazole-5-carboxylic acid (Example 69),
1-cyclopentyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 70),
1-cyclopentyl-2-(4-phenethyloxyphenyl)benzimidazole-5-carboxylic acid (Example 71),
trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-tert-butylcyclohexane (Example 72),
2-(4-benzyloxyphenyl)-5-carboxymethoxy-1-cyclopentylbenzimidazole (Example 73),
2-(4-benzylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 74),
2-[4-(N-benzenesulfonyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 75),
2-[4-(N-benzyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 76),
1cyclohexyl-2-(4-phenethylphenyl)benzimidazole-5-carboxylic acid (Example 77),
2-(1-benzyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 78),
2-(1-benzoyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 79),
1-cyclopentyl-2-[1-(p-toluenesulfonyl)-4-piperidyl]-benzimidazole-5-carboxylic acid (Example 80),
1-cyclohexyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 81),
1-cyclohexyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 82),
1-cyclohexyl-2-[4-(3,5-di-tert-butylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid (Example 83),
2-(4-benzyloxyphenyl)-1-(4-methylcyclohexyl)benzimidazole-5-carboxylic acid (Example 84),
1-cyclohexyl-2-{4-[2-(2-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 85),
1-cyclohexyl-2-[4-(1-naphthyl)methoxyphenyl]benzimidazole-5-carboxylic acid (Example 86),
1-cyclohexyl-2-[4-(dibenzylamino)phenyl]benzimidazole-5-carboxylic acid (Example 87),
2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 88),
2-(4-benzyloxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 89),
1-cyclohexyl-2-[4-(dibenzylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 90),
2-(4-benzoylmethoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 91),
2-(4-benzyl-1-piperazinyl)-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 92),
1-cyclohexyl-2-[4-(3,3-diphenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 93),
2-[4-(3-chloro-6-phenylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 94),
2-(4-benzyloxypiperidino)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 95),
1-cyclohexyl-2-{4-[2-(phenoxy)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 96),
1-cyclohexyl-2-[4-(3-phenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 97),
1-cyclohexyl-2-[4-(5-phenylpentyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 98),
2-(3-benzyloxy-5-isoxazolyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 99),
2-(2-benzyloxy-5-pyridyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 100),
1-cyclohexyl-2-{4-[2-(3,4, 5-trimethoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 101),
2-(4-benzyloxyphenyl)-1-(4, 4-dimethylcyclohexyl)benzimidazole-5-carboxylic acid (Example 102),
1-cyclohexyl-2-{4-[2-(1-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 103),
2-[4-(2-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidiazole-5-carboxylic acid (Example 104),
2-[4-(3-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 105),
1-cyclohexyl-2-[4-(2-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 106),
1-cyclohexyl-2-[4-(3-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 107),
1-cyclohexyl-2-[4-(2-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 108),
1-cyclohexyl-2-[4-(3-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 109),
1-cyclohexyl-2-[4-(2-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 110),
1-cyclohexyl-2-[4-(3-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 111),
1-cyclohexyl-2-{4-[2-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 112),
1-cyclohexyl-2-{4-[3-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 113),
1-cyclohexyl-2-[4-(2-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 114),
1-cyclohexyl-2-[4-(3-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 115),
1-cyclohexyl-2-{4-[2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 116),
1-cyclohexyl-2-{4-[2-(4-trifluoromethylphenyl)benzyloxy]-phenyl}benzimidazole-5-carboxylic acid (Example 117),
2-{4-[bis(4-chlorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 118),
1-cyclohexyl-2-{4-[2-(4-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 119),
1-cyclohexyl-2-{4-[2-(2-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 120),
1-cyclohexyl-2-{4-[2-(3-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 121),
2-(4-benzyloxyphenyl)-1-cycloheptylbenzimidazole-5-carboxylic acid (Example 122),
1-cyclohexyl-2-[4-(2-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 123),
1-cyclohexyl-2-[4-(3-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 124),
1-cyclohexyl-2-[4-(2,2-diphenylethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 125),
2-(4-benzyloxyphenyl)-1-(3-cyclohexenyl)benzimidazole-5-carboxylic acid (Example 126),
cis-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-fluorocyclohexane (Example 127),
1-cyclohexyl-2-[4-(2-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 128),
1-cyclohexyl-2-[4-(3-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 129),
2-{4-[(2R)-2-benzyloxycarbonylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 1301,
1-cyclohexyl-2-{2-fluoro-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 131),
2-[4-(4-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 132),
2-{4-[bis(4-methylphenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 133),
2-{4-[bis(4-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 134),
1-cyclohexyl-6-methoxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 135),
1-cyclohexyl-6-hydroxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 136),
1-cyclohexyl-6-methyl-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 137),
2-{4-[2-(2-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 138),
2-{4-[2-(3-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 139),
2-[4-(2-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 140),
2-[4-(3-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 141),
2-{4-[3-chloro-6-(4-methylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 142),
2-{4-[3-chloro-6-(4-methoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 143),
1-cyclohexyl-2-{2-methyl-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 144),
2-{4-[2-(4-tert-butylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 145),
2-{4-(3-chloro-6-phenylbenzyloxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 146),
2-{4-[3-chloro-6-(3,5-dichlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 147),
2-{4-[bis(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 148),
2-{4-(4-benzyloxyphenoxy)-2-chlorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 149),
2-{4-(4-benzyloxyphenoxy)-2-trifluoromethylphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 150),
2-{4-[3-chloro-6-(2-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 1511,
2-{4-[(2R)-2-amino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 1521,
2-[4-(2-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 153),
2-[4-(3-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 154),
2-{4-[2-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 155),
2-{4-[3-1 (1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 156),
2-{4-[3-chloro-6-(3,4,5-trimethoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 157),
2-{4-[2-(2-biphenylyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 158),
2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 159),
1-cyclohexyl-2-{4-[2-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride (Example 160),
1-cyclohexyl-2-{4-[3-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride (Example 161),
2-{4-[(2R)-2-acetylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 162),
1-cyclohexyl-2-{4-[3-(4-methyl-3-pentenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 163),
1-cyclohexyl-2-{4-[3-(3-methyl-3-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 164),
2-{4-[{(2S)-1-benzyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 165)
2-{4-[3-chloro-6-(4-methylthiophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 166),
2-{4-[3-chloro-6-(4-methanesulfonylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 167),
2-{4-[3-chloro-6-(2-thienyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 168),
2-{4-[3-chloro-6-(3-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 169),
2-{4-[3-chloro-6-(3-pyridyl)benzyloxy]phenyl}7-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 170),
2-{4-[3-chloro-6-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 171),
2-[4-(4-benzyloxyphenoxy)-3-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 172),
2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 173),
2-{4-[3-chloro-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 174),
2-{4-[2-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 175),
2-{4-[3-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 176),
1-cyclohexyl-2-{4-[3-(2-propynyloxy)phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 177),
1-cyclohexyl-2-{4-[3-(3-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 178),
2-(4-benzyloxy-2-methoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 179),
2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 180),
2-[4-(carboxydiphenylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 181),
2-{4-[2-(4-chlorophenyl)-5-nitrobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 182),
2-{4-[3-acetylamino-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 183),
2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 184),
2-{4-[{(2S)-1-benzyloxycarbonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 185),
2-{2-chloro-4-[2-(4-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 186),
1-cyclohexyl-2-{4-[3-(2-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 187),
2-{4-[2-(4-chlorophenyl)-5-fluorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 188),
2-{4-[3-carboxy-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 189),
2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 190),
1-cyclohexyl-2-{4-[2-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 191),
1-cyclohexyl-2-{4-[2-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 192),
2-{4-[{(2S)-1-benzenesulfonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 193),
2-{4-[{(2S)-1-benzoyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 194),
2-{4-[2-(4-carbamoylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 195),
1-cyclohexyl-2-{4-[3-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 196),
1-cyclohexyl-2-{4-[3-(piperidinocarbonylmethoxy)phenol]-phenyl}benzimidazole-5-carboxylic acid (Example 197),
1-cyclohexyl-2-{4-[3-{(1-methanesulfonyl-4-piperidyl)methoxy}-phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 198),
1-cyclohexyl-2-{4-[{2-methyl-5-(4-chlorophenyl)-4-oxazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 199),
2-{4-[3-(3-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 200),
2-{4-[3-(4-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 201),
1-cyclohexyl-2-{4-[3-(4-fluorobenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 202),
1-cyclohexyl-2-{4-[{(2S)-1-(4-nitrophenyl)-2-pyrrolidinyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 203),
1-cyclohexyl-2-{4-[{(2S)-1-phenyl-2-pyrrolidinyl}methoxy]-phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 204),
2-{4-[{(2S)-1-(4-acetylaminophenyl)-2-pyrrolidinyl}methoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 205),
2-{4-[{5-(4-chlorophenyl)-2-methyl-4-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 206),
2-{4-[bis(3-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 207),
1-cyclohexyl-2-{4-[2-(4-chlorophenyl)-3-nitrobenzyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 208),
1-cyclohexyl-2-{4-[3-(4-tetrahydropyranyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 209),
1-cyclohexyl-2-{4-[3-(4-trifluoromethylbenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 210),
1-cyclohexyl-2-{4-[3-{(1-methyl-4-piperidyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 211),
2-{4-[3-(4-tert-butylbenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 212),
2-{4-[3-(2-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 213),
1-cyclohexyl-2-{4-[3-(3-pyridyl)phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 214),
2-{4-[3-(4-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 215),
1-cyclohexyl-2-{4-[3-(4-methoxyphenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 216),
1-cyclohexyl-2-{4-[4-(4-methanesulfonylphenyl)-2-methyl-5-thiazolyl methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 217),
2-{4-[{4-(4-chlorophenyl)-2-methyl-5-thiazolyl}ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 218),
2-{4-[1-(4-chlorobenzyl)-3-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 219),
1-cyclohexyl-2-{4-[3-{(2-methyl-4-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 220),
1-cyclohexyl-2-{4-[3-{(2,4-dimethyl-5-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 221),
1-cyclohexyl-2-{4-[3-(3,5-dichlorophenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 222),
2-{4-[1-(4-chlorobenzyl)-4-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 223),
2-{4-[3-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 224),
2-{4-[4-carbamoyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 225),
2-{4-[4-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 226),
2-{4-[3-{(2-chloro-4-pyridyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 227),
2-{4-[{(2S)-1-(4-dimethylcarbamoylphenyl)-2-pyrrolidinyl}-methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 228),
2-{4-[2-(4-chlorophenyl)-5-ethoxycarbonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 229),
1-cyclohexyl-2-[4-(3-trifluoromethylphenoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 230),
1-cyclohexyl-2-{4-[{4-(4-dimethylcarbamoylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 231),
2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 232),
2-{4-[{4-(4-chlorophenyl)-2-methyl-5-pyrimidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 233),
2-{4-[{2-(4-chlorophenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 234),
2-{4-[{3-(4-chlorophenyl)-2-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 235),
2-{4-[2-(3-chlorophenyl)-4-methylamino-1,3,5-triazin-6-yloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate (Example 236),
2-{4-[2-(4-chlorophenyl)-4-(5-tetrazolyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 237),
2-[4-(4-benzyloxy-6-pyrimidinyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 238),
1-cyclohexyl-2-{4-[4-(4-pyridylmethoxy)-6-pyrimidinyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 239),
2-{4-[4-(3-chlorophenyl)-6-pyrimidinyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 2401,
methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 241),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 242),
ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 243),
methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 244),
methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 245),
methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (Example 246),
methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 247),
2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 248),
2-{4-[3-(tert-butylsulfamoyl)-6-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 249),
2-{4-[2-(4-chlorophenyl)-5-sulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate (Example 250),
2-(4-benzyloxycyclohexyl)-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 251),
2-[2-(2-biphenylyloxymethyl)-5-thienyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 252),
2-[2-(2-biphenylyloxymethyl)-5-furyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 253),
1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-hydroxymethyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 254),
1-cyclohexyl-2-{4-[{4-(4-carboxyphenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 255),
1-cyclohexyl-2-{2-fluoro-4-[4-fluoro-2-(3-fluorobenzoyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 256),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-sulfonic acid (Example 257),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexylbenzimidazole-4-carboxylic acid (Example 258),
1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-5-(4-pyridylmethoxy)phenoxy]phenyl}benzimidazole-5-carboxylic acid dihydrochloride (Example 259),
1-cyclohexyl-2-{4-[3-carboxy-5-(4-pyridylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid dihydrochloride (Example 260),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-4-carboxylic acid (Example 261),
2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 262),
2-{4-[{2-(4-carboxyphenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 263),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 264),
2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 265),
1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-trifluoromethylphenyl)benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 266),
1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-methylthiophenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 267),
2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 268),
2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 269),
2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 270),
2-{4-[3-dimethylcarbamoyl-6-(4-methanesulfonylphenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 271),
2-{4-[3-dimethylcarbamoyl-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 272),
2-{4-[3-dimethylcarbamoyl-6-(4-dimethylcarbamoylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 273),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 274),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 275),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 276),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 277),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 278),
2-{4-[2-(4-chlorophenyl)-5-dimethylsulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 279),
2-{4-[2-(4-chlorophenyl)-5-methanesulfonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 280),
methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (Example 281),
2-{4-[2-(4-chlorophenyl)-5-dimethylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 282),
2-{4-[2-(4-chlorophenyl)-5-methanesulfonylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 283),
2-{4-[2-(4-chlorophenyl)-5-diethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 284),
2-{4-[2-(4-chlorophenyl)-5-isopropylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 285),
2-{4-[2-(4-chlorophenyl)-5-piperidinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 286),
2-{4-[2-(4-chlorophenyl)-5-(1-pyrrolidinyl)carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 287),
2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethyl)carbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 288),
2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidino)-carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 289),
2-{4-[2-(4-chlorophenyl)-5-morpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 290),
2-{4-[2-(4-chlorophenyl)-5-thiomorpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 291),
2-{4-[3-(carboxymethylcarbamoyl)-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 292),
2-{4-[2-{4-(2-carboxyethyl)phenyl}-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 293),
2-{4-[3-chloro-6-(4-hydroxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 294),
2-{4-[3-chloro-6-(4-methoxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 295),
2-{4-[2-(3-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 296),
2-{4-[2-(4-chlorophenyl)-5-methylthiobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 297),
2-{4-[2-(4-chlorophenyl)-5-methylsulfinylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 298),
2-{4-[2-(4-chlorophenyl)-5-cyanobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 299),
2-{4-[bis(3-pyridyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 300),
2-{4-[bis(4-dimethylcarbamoylphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 301),
sodium 2-{4-[2-thienyl-3-thienylmethoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 302),
methyl 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 303),
sodium 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 304),
2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 305),
2-{4-[2-(4-carboxyphenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 306),
2-{4-[2-(4-carbamoylphenyl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 307),
2-{4-[5-amino-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 308),
2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 309),
2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfonyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 310),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzylthio]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 311),
2-{4-[bis(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 312),
2-[4-(phenyl-3-pyridylmethoxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 313),
methyl 2-{4-[2-(4-chlorophenyl)-5-(methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 314),
2-{4-[5-chloro-2-(4-pyridyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 315),
2-{4-[2-(4-chlorophenyl)-5-(benzylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 316),
2-{4-[2-(4-chlorophenyl)-5-(cyclohexylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 317),
2-{4-[2-(4-chlorophenyl)-5-(4-pyridylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 318),
2-{4-[2-(4-chlorophenyl)-5-(N-benzyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 319),
methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate (Example 501),
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic acid (Example 502),
2-(4-benzyloxyphenyl)-1-cyclopentyl-1H-indole-5-carboxylic acid (Example 503),
ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate (Example 601),
2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid (Example 602), and
2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (Example 701).
(92) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of
2-{4-[5-dimethylaminocarbonyl-2-(4-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 320),
2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperazin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 321),
2-{4-[2-(4-chlorophenyl)-5-{N-(3-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 322),
2-{4-[2-(4-chlorophenyl)-5-{N-(2-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 323),
2-{4-[2-(4-chlorophenyl)-5-(cyclohexylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 324),
2-{4-[2-(4-chlorophenyl)-5-(2-pyridin-4-ylethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 325),
2-{4-[(4-fluorophenyl){4-(dimethylaminocarbonyl)phenyl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 326),
2-{4-[(4-fluorophenyl)(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 327),
2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 328),
2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 329),
2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 330),
2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 331),
2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 332),
2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 333),
2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 334), and
2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 335).
(93) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of
methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 336),
methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 337),
methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 338),
methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 339),
2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 340),
2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 341),
2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 342),
2-{4-[2-(4-chlorophenyl)-5-{(4-hydroxypiperidin-1-ylcarbonyl)-methoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 343),
2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 344),
2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 345),
2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 346),
2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-cyclohexylbenzimidazole-5-carboxylic acid (Example 347),
2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 348),
2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazole)-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 349),
2-{4-[2-(4-chlorophenyl)-4-((isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 350),
2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 351),
2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 352),
2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 353),
2-4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 354),
2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 355),
2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 356),
2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 357),
2-{4-[5-(2-aminothiazol-4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 358),
2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 359),
2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 360),
2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 361),
2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 362),
2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 363)
2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}7-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 364),
2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 365),
2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 366),
2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 367),
2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 368),
2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 369),
2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl) ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 370),
2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 371),
2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 372),
2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 373),
2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 374),
2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadimazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 375),
2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 376),
2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 377),
2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 378),
2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 379),
2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 380),
2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 381),
2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 382),
2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 383),
2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 384),
2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 385),
2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 386),
2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 387),
2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 388),
2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic ac-id hydrochloride (Example 389),
2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 390),
2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 391),
2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 392),
2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 393),
2-{4-[2-(4-chlorophenyl)-5-{(ethylcarbamoyl)amino benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 394),
2-{4-[2-(4-chlorophenyl)-5-{(isopropylcarbamoyl) amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 395),
2-{4-[2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 396),
2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 397),
2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 398),
2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 399),
2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 400),
2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 401),
2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 402),
2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 403),
2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 404),
2-{4-[2-{4-(methylthio)phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 405),
2-{4-[2-{4-(methylthio)phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 406),
2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazol(s-5-carboxylic acid hydrochloride (Example 407),
2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 408),
2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 409),
2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 410),
2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 411),
2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 412),
2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 413)
2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxyphenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 414)
2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 415),
2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 416),
2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 417),
2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 418),
2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 419),
2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid hydrochloride (Example 420),
2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid (Example 421),
2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 422),
2-{4-[2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 423),
2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 424),
2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 425),
2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl}ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 426),
2-{4-{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 427),
2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl}ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 428),
2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-yl}ethoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 429),
2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole)-carboxylic acid hydrochloride (Example 430),
2-{4-[{2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5)-carboxylic acid hydrochloride (Example 431),
2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}ethoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 432),
2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 433),
2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole (Example 434),
2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole hydrochloride (Example 435),
2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzimidazole hydrochloride (Example 436),
2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 437),
2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 438),
2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}-methyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 439),
2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 440),
2-3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 441),
2-{4-[(3-dimethylcarbamoylphenyl)(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 442),
2-{4-[{3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 443),
1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-xcex2-D-glucuronic acid (Example 444),
{[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-xcex2-D-glucuronic acid (Example 445),
2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 446),
2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-dimidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride (Example 702), and
2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride (Example 703).
(94) A pharmaceutical composition comprising a fused ring compound of any of (42) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
(95) A hepatitis C virus polymerase inhibitor comprising a fused ring compound of any of (1) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
(96) An anti-hepatitis C virus agent comprising a fused ring compound of any of (1) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
(97) A therapeutic agent for hepatitis C comprising a fused ring compound of any of (42) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
(98) An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of (96) above and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.
(99) An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of (96) above and (b) interferon.
(100) A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of (95) above and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.
(101) A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of (95) above and (b) interferon.
(102) A benzimidazole compound of the following formula [III]
wherein Ra36 is hydrogen atom or carboxyl-protecting group, Ra37 is cyclopentyl or cyclohexyl, and Ra38 is hydrogen atom or fluorine atom, or a salt thereof.
(103) A thiazole compound selected from the group consisting of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and 4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole, or a pharmaceutically acceptable salt thereof.
(104) A pharmaceutical composition comprising (a) the fused compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof and (b) at least one agent selected from the group consisting of an antiviral agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.
(105) A pharmaceutical composition comprising (a) the fused compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof and (b) interferon.
(106) A method for treating hepatitis C, which comprises administering an effective amount of a fused ring compound of the formula [I] of (1) above, or a pharmaceutically acceptable salt thereof.
(107) The method of (106) above, further comprising administering an effective amount of at least one agent selected from the group consisting of an antiviral agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.
(108) The method of (106) above, further comprising administering an effective amount of interferon.
(109) A method for inhibiting hepatitis C virus polymerase, which comprises administering an effective amount of a fused ring compound of the formula [I] of (1) above, or a pharmaceutically acceptable salt thereof.
(110) The method of (109) above, further comprising administering an effective amount of at least one agent selected from the group consisting of an antiviral agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.
(111) The method of (109) above, further comprising administering an effective amount of interferon.
(112) Use of a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof for the production of a pharmaceutical agent for treating hepatitis C.
(113) Use of a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof for the production of a hepatitis C virus polymerase inhibitor.
(114) A pharmaceutical composition for the treatment of hepatitis C, which comprises a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
(115) A pharmaceutical composition for inhibiting hepatitis C virus polymerase, which comprises a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
(116) A commercial package comprising a pharmaceutical composition of (114) above and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for treating hepatitis C.
(117) A commercial package comprising a pharmaceutical composition of (115) above and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for inhibiting hepatitis C virus polymerase.
The definitions of respective substituents and moieties used in the present specification are as follows.
The halogen atom is a fluorine atom, chlorine atom, bromine atom or iodine atom, preferably fluorine atom, chlorine atom or bromine atom.
Particularly preferably, the halogen atom is fluorine atom at R5, R5xe2x80x2, R6, R6xe2x80x2, group A and group C, and fluorine atom or chlorine atom at X, Z, Zxe2x80x2, group B and group D.
The C1-6 alkyl is straight chain or branched chain alkyl having 1 to 6 carbon atoms, and is exemplified by methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, hexyl and the like.
Preferably, it is straight chain or branched chain alkyl having 1 to 4 carbon atoms, and is particularly preferably methyl at Ra7, Ra8, Ra9, Ra15, Ra16, Ra17, Ra29, Ra33, Ra35, Rb6 and Rb7 and methyl or tert-butyl at Rb1, Rb2, group B and group C.
The halogenated C1-6 alkyl is the above-defined C1-6 alkyl except that it is substituted by the above-defined halogen atom. Preferably, it is halogenated alkyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include fluoromethyl, difluoromethyl, trifluoromethyl, bromomethyl, chloromethyl, 1,2-dichloromethyl, 2,2-dichloromethyl, 2,2,2-trifluoroethyl and the like.
The halogenated C1-6 alkyl is particularly preferably trifluoromethyl at group B.
The C1-6 alkylene is straight chain alkylene having 1 to 6 carbon atoms, and is exemplified by methylene, ethylene, trimethylene, tetramethylene, pentamethylene or hexamethylene.
The C1-6 alkylene is preferably methylene or ethylene at Y.
The C2-6 alkenylene is straight chain alkenylene having 2 to 6 carbon atoms, and is exemplified by vinylene, propenylene, 1-butenylene, 1,3-butadienylene and the like.
The C2-6 alkenylene is preferably vinylene at Y.
The C1-6 alkoxy is alkyloxy wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it: is alkoxy wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methoxy, ethoxy, propoxy, isopropyloxy, butoxy, isobutyloxy, tert-butyloxy, pentyloxy, hexyloxy and the like.
The C1-6 alkoxy is particularly preferably methoxy at Ra2 Ra3, Ra27, Ra28, Ra33, group A and group C.
The C1-6 alkoxy C1-6 alkoxy is that wherein C1-6 alkoxy in the above definition is substituted by C1-6 alkoxy defined above and is preferably that wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Specific examples include methoxymethyl, ethoxymethyl, methoxyethoxy, methoxypropoxy, isopropyloxyethoxy and the like.
The group A is particularly preferably methoxyethoxy.
The C1-6 alkanoyl is alkylcarbonyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkanoyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include acetyl, propionyl, butyryl, isobutyryl, pivaloyl and the like.
The C1-6 alkanoyl is particularly preferably acetyl at R1, R2, R3, R4, Ra5, Ra29, Rb7 and group B.
The C1-6 alkoxycarbonyl is alkyloxycarbonyl wherein the alkoxy moiety thereof is the above-defined C1-6 alkoxy. Preferably, it is alkoxycarbonyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropyloxycarbonyl, butoxycarbonyl, isobutyloxycarbonyl, tert-butyloxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and the like.
The C1-6 alkoxycarbonyl is particularly preferably methoxycarbonyl or ethoxycarbonyl at Ra10 and group A.
The C1-6 alkylamino is alkylamino or dialkylamino wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkylamino or dialkylamino wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, methylethylamino, N-isopropyl-N-isobutylamino and the like.
The C1-6 alkylamino is particularly preferably methylamino at Ra7, and particularly preferably dimethylamino at Ra21 and group A, and particularly preferably dimethylamino, ethylamino or isopropylamino at Ra24.
The C1-6 alkanoylamino is alkylcarbonylamino wherein the alkanoyl moiety thereof is the above-defined C1-6 alkaroyl. Preferably, it is alkylcarbonylamino wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include acetylamino, propionylamino, butyrylamino, isobutyrylamino, pivaloylamino and the like.
The C1-6 alkanoylamino is particularly preferably acetylamino at X and Ra10.
The C1-6 alkylsulfonyl is alkylsulfonyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkylsulfonyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl and the like.
The C1-6 alkylsulfonyl is particularly preferably methylsulfonyl at X and Ra5.
The C6-14 aryl is aromatic hydrocarbon having 6 to 14 carbon atoms. Examples thereof include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl and the like.
The C6-14 aryl is preferably phenyl or naphthyl, particularly preferably phenyl at the ring A, ring Axe2x80x2, ring B and ring Bxe2x80x2.
The C3-8 cycloalkyl is saturated cycloalkyl having 3 to 8, preferably 5 to 7, carbon atoms. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
The C3-8 cycloalkyl is particularly preferably cyclohexyl at the ring A, ring Axe2x80x2, ring B and ring Bxe2x80x2.
The C3-8 cycloalkenyl is cycloalkenyl having 3 to 8, preferably 5 to 7, carbon atoms and has at least 1, preferably 1 or 2, double bond(s). Examples thereof include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohecenyl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, cycloheptenyl and cyclooctenyl and the like, but do not include aryl (e.g., phenyl) or completely saturated cycloalkyl.
The C3-8 cycloalkenyl is preferably cyclohexenyl at the ring A and ring Axe2x80x2.
The heterocyclic group has, as an atom constituting the ring, 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, besides a carbon atom,, and includes saturated ring and unsaturated ring, monocyclic ring and fused ring having the number of ring atom constituting the ring of 3 to 14.
The heterocyclic group as a monocyclic ring includes, for example, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl and the like.
The heterocyclic group includes the groups of the following formulas. 
wherein E1 is an oxygen atom, a sulfur atom or N(xe2x80x94Ra35) E2 is an oxygen atom, CH2 or N(xe2x80x94Ra35), E3 is an oxygen atom or a sulfur atom, wherein Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and hxe2x80x2 are the same or different and each is an integer of 1 to 3.
Specific examples of the heterocyclic group include 
and the like.
Examples of the heterocyclic group as a fused ring include quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydro-2-oxobenzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl and the like.
Preferably, it is a heterocyclic group which is a 5-membered or a 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl 
and the like.
At R1, R2, R3, R4, Z and group D, tetrazolyl and 5-oxo-xcex942-1,2,4-oxadiazolin-3-yl are particularly preferable.
The heterocyclic group is preferably pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl which is an aromatic group, and particularly preferably pyridyl at the ring A and ring Axe2x80x2.
The heterocyclic group is particularly preferably pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or thiadiazolyl, which is an aromatic group, at the ring B and ring Bxe2x80x2. More preferably it is pyridyl or thiazolyl, most preferably thiazolyl.
The C6-14 aryl C1-6 alkyl is arylalkyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl and the aryl moiety is the above-defined C6-14 aryl. Preferably, it is arylalkyl wherein the alkyl moiety thereof is straight chain alkyl having 1 to 4 carbon atoms and the aryl moiety is phenyl. Examples thereof include benzyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl and the like.
The C6-14 aryl C1-6 alkyl is particularly preferably benzyl at Ra8 and Rb6.
The glucuronic acid residue is glucuronic acid less any hydroxyl group, preferably P-D-glucuronic acid substituted at 1-position.
The C6-14 aryl C1-6 alkyloxycarbonyl is arylalkyloxycarbonyl wherein the C6-14 aryl C1-6 alkyl moiety thereof is the above-defined C6-14 aryl C1-6 alkyl. Preferably, it is arylalkyloxycarbonyl wherein the alkyl moiety thereof is straight chain alkyl having 1 to 4 carbon atoms and the aryl moiety is phenyl. Examples thereof include benzyloxycarbonyl, phenethyloxycarbonyl, 3-phenylpropyloxycarbonyl, 2-phenylpropyloxycarbonyl, 4-phenylbutyloxycarbonyl and the like.
The C6-14 aryl C1-6 alkyloxycarbonyl is particularly preferably benzyloxycarbonyl at Rb7.
The optionally substituted C1-6 alkyl is the above-defined C1-6 alkyl, preferably that wherein straight chain or branched chain alkyl having 1 to 4 carbon atoms is optionally substituted with 1 to 3 substituent(s), and includes unsubstituted alkyl. The substituent(s) is(are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino, the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxy C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples of optionally substituted C1-6 alkyl include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, neopentyl, 1-ethylpropyl, hexyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 1-hydroxy-1-methylethyl, 1-hydroxypropan-2-yl, 1,3-dihydroxypropan-2-yl, 1-hydroxy-2-methylpropan-2-yl, carboxylmethyl, 2-carboxylethyl, methoxymethyl, methoxyethyl, methoxyethoxyethyl, ethoxycarbonylmethyl, 2-ethoxycarbonylethyl, 2-dimethylaminoethyl and the like.
Preferably, the optionally substituted C1-6 alkyl is methyl, 1-hydroxy-1-methylethyl, carboxylmethyl or 2-dimethylaminoethyl at R1, R2, R3 and R4, methyl or trifluoromethyl at R5, R5xe2x80x2, R6 and R6xe2x80x2, methyl at R7, R8, Ra25, Ra31 and R5, methyl, ethyl or isopropyl at Ra24, methyl or isopropyl at Ra18, methyl or ethyl at Ra1 and Ra19, methyl, carboxylmethyl or 2-dimethylaminoethyl at Ra2 and Ra3, methyl or carboxylmethyl at Ra6, methyl, ethyl, isopropyl, butyl or trifluoromethyl at X, methyl, ethyl, isopropyl, butyl, isobutyl, tert-butyl, isopentyl, neopentyl, 1-ethylpropyl or carboxylmethyl at Ra10, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, trifluoromethyl, 2-hydroxyethyl or carboxylmethyl at Ra11, methyl or 4-hydroxybutyl at Ra12, methyl, ethyl, isopropyl, butyl, 2-hydroxyethyl, 4-hydroxybutyl, ethoxycarbonylmethyl, 2-(ethoxycarbonyl)ethyl or 2-dimethylaminoethyl at Ra13, methyl, propyl, butyl, isopentyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, methoxyethyl, methoxyethoxyethyl or carboxymethyl at Ra20, methyl or ethyl at Ra22 and Ra23, methyl isopropyl or tert-butyl at Ra26, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, 2-hydroxyethyl 1-hydroxypropan-2-yl, 1-hydroxy-2-methylpropan-2-yl or carboxylmethyl at Ra27 and Ra28, and methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 2-carboxylethyl, methoxymethyl or ethoxycarbonylmethyl at Z, Zxe2x80x2 and group D.
It is particularly preferably, trifluoromethyl at R5, R5xe2x80x2, R6 and R6, methyl or tert-butyl at Ra26, methyl, tert-butyl, trifluoromethyl or hydroxymethyl at Z, Zxe2x80x2 and group D, and methyl at other substituents.
The optionally substituted C2-6 alkenyl is that wherein straight chain or branched chain alkenyl having 2 to 6 carbon atoms is optionally substituted by 1 to 3 substituent(s), and includes unsubstituted alkenyl. The substituent(s) is (are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino, the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxy C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples of optionally substituted C2-6 alkenyl include vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 1,3-butadienyl, 2-isopentenyl, 3-isohexenyl, 4-methyl-3-pentenyl, 2-carboxylethenyl and the like.
The optionally substituted C2-6 alkenyl is preferably 2-carboxylethenyl at X, and preferably 2-isopentenyl, 3-isohexenyl or 4-methyl-3-pentenyl at Ra20.
The optionally substituted C2-6 alkynyl is that wherein straight chain or branched chain alkynyl having 2 to 6 carbon atoms is optionally substituted by 1 to 3 substituent(s), and includes unsubstituted alkynyl. The substituent(s) is(are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino, the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples thereof include ethynyl, 1-propynyl, 2-propynyl, 3-butynyl and the like.
The optionally substituted C2-6 alkynyl is preferably 2-propynyl at Ra20.
The C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined C6-14 aryl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the above-defined halogen atom, cyano, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, xe2x80x94(CH2)rxe2x80x94COORb1, xe2x80x94(CH2)rxe2x80x94CONRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1xe2x80x94CORb2, xe2x80x94(CH2)rxe2x80x94NHSO2Rb1, xe2x80x94(CH2)rxe2x80x94ORb1, xe2x80x94(CH2)rxe2x80x94SRb1, xe2x80x94(CH2)rxe2x80x94SO2Rb1 and xe2x80x94(CH2)rxe2x80x94SO2NRb1Rb2 (wherein Rb1 and Rb2 are each independently hydrogen atom or the above-defined C1-6 alkyl and r is 0 or an integer of 1 to 6).
Examples thereof include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, pentafluorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-nitrophenyl, 4-cyanophenyl, 4-acetylphenyl, 4-carboxylphenyl, 4-carbamoylphenyl, 4-aminophenyl, 4-dimethylaminophenyl, 4-acetylaminophenyl, 4-(methylsulfonylamino)phenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-methylthiophenyl, 4-methylsulfonylphenyl, 4-aminosulfonylphenyl, 3-nitro-4-methoxyphenyl and 4-nitro-3-methoxyphenyl.
The aryl moiety is preferably phenyl, the group B here is preferably the above-defined halogen atom, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl or xe2x80x94(CH2)rxe2x80x94ORb1. Examples of group B include fluorine atom, chlorine atom, nitro, methyl, tert-butyl, trifluoromethyl and methoxy. Particularly preferably, it is fluorine atom or chlorine atom.
With regard to xe2x80x9cC6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group Bxe2x80x9d, it is preferably phenyl, 4-tert-butylphenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-methoxyphenyl or 4-trifluoromethylphenyl at Ra12, Ra27 and Ra28, phenyl at Ra14, Ra22, Ra23, Ra26 and Rb5, phenyl or 3-fluorophenyl at Ra18, phenyl or 2,4-dichlorophenyl at Ra20, phenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 3,5-dichlorophenyl, 3-nitro-4-methoxyphenyl or 4-nitro-3-methoxyphenyl at Ra24, and phenyl or 4-methylphenyl at Ra25.
It is particularly preferably phenyl at other substituents.
The C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C6-14 aryl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the above-mentioned group D (substituents shown under (a) to (q)).
Examples of group D here include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, propyloxy, isopropyloxy, isopentyloxy, 2-isopentenyloxy, 3-isohexenyloxy, 4-methyl-3-pentenyloxy, 2-propynyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl and tetrazolyl.
Examples of C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 4-bromophenyl, 4-nitrophenyl, pentafluorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, 4-acetylaminophenyl, 4-cyanophenyl, 4-acetylphenyl, 4-aminophenyl, 4-dimethylaminophenyl, 4-(methylsulfonylamino)phenyl, 4-methylsulfinylphenyl, 4-aminosulfonylphenyl and 3-nitro-4-methoxyphenyl, 4-nitro-3-methoxyphenyl and 4-tetrazol-5-ylphenyl.
At Z and Zxe2x80x2, the aryl moiety is preferably phenyl, and group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, xe2x80x94(CH2)txe2x80x94COORa19, xe2x80x94(CH2)tCONRa27Ra28, xe2x80x94(CH2)txe2x80x94ORa20, xe2x80x94(CH2)txe2x80x94NRa29COxe2x80x94Ra24, xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 or xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26.
Examples of C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D preferably include phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, 4-acetylaminophenyl, 4-methylsulfinylphenyl, 4-aminosulfonylphenyl, 4-cyanophenyl and 4-tetrazolylphenyl.
Particularly preferably, it is the above-defined halogen atom, the above-defined optionally substituted C1-6 alkyl, xe2x80x94(CH2)txe2x80x94COORa19, xe2x80x94(CH2)txe2x80x94CONRa27Ra28, xe2x80x94(CH2)txe2x80x94ORa20 or xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25, which is specifically fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino. More preferably, it is fluorine atom, chlorine atom, m(ethyl, tert-butyl, carboxyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino, most preferably fluorine atom or chlorine atom.
The heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined heterocyclic group is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocyclic group. The substituent(s) is(are) selected from the above-defined halogen atom, cyano, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, xe2x80x94(CH2)rCOORb1, xe2x80x94(CH2)rxe2x80x94CONRb1Rb2, xe2x80x94(CH2)rxe2x80x94NRb1Rb2, xe2x80x94(CH2)rxe2x80x94NR b1xe2x80x94CORb2, xe2x80x94(CH2)rxe2x80x94NHSO2Rb1, xe2x80x94(CH2)rxe2x80x94ORb1, xe2x80x94(CH2)rxe2x80x94SRb1, xe2x80x94(CH2)rxe2x80x94SO2Rb1 and xe2x80x94(CH2)rxe2x80x94SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or the above-defined C1-6 alkyl and r is 0 or an integer of 1 to 6.
Examples thereof include 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 4-chloropyridin-3-yl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, 2-thienyl, 3-thienyl, furyl, oxazolyl, 2-methyloxazol-4-yl, isoxazolyl, thiazolyl, 2-methylthiazol-4-yl, 2,5-dimethylthiazol-4-yl, 2,4-dimethylthiazol-5-yl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, 3-hydroxypyrrolidinyl, imidazolidinyl, azetidinyl, piperidyl, 3-hydroxypiperidino, 4-hydroxypiperidino, 3,4-dihydroxypiperidino, 4-methoxypiperidino, 4-carboxypiperidino, 4-(hydroxymethyl)piperidino, 2-oxopiperidino, 4-oxopiperidino, 2,2,6,6-tetramethylpiperidino, 2,2,6,6-tetramethyl-4-hydroxypiperidino, N-methylpiperidin-4-yl, N-(tert-butoxycarbonyl)piperidin-4-yl, N-acetylpiperidin-4-yl, N-methylsulfonylpiperidin-4-yl, piperazinyl, 4-methylpiparazinyl, 4-methylsulfonylpiperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl, tetrahydropyranyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolyl, benzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl, 
and the like.
The heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or a 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridiazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the group B here is preferably the above-defined halogen atom, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, xe2x80x94(CH2)rxe2x80x94COORb1, xe2x80x94(CH2)rxe2x80x94CONRb1Rb2 or xe2x80x94(CH2)rxe2x80x94ORb1.
Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group B preferably include piperidino, 4-methylpiperidino, 2,6-dimethylpiperidino, 4-hydroxypiperidino, 1-piperazinyl, 1-(methylsulfonyl)piperidin-4-yl, 1-pyrrolidinyl, morpholino, 4-thiomorpholinyl, tetrahydropyranyl, pyridyl, thiazolyl, 
Particularly preferably, it is piperidino, 4-methylpiperidino, 2,6-dimethylpiperidino, 4-hydroxypiperidino, 1-piperazinyl, 1-pyrrolidinyl, morpholino or 4-thiomorpholinyl at Ra18, tetrahydropyranyl or 4-hydroxypiperidino at Ra20, piperidino, 4-hydroxypiperidino or 3,4-dihydroxypiperidino at Ra21, pyridyl or morpholino at Ra24, pyridyl or 4-hydroxypiperidino at Ra25, pyridyl or thiazolyl at Ra26 and at Ra27 and Ra28, it is 1-(methylsulfonyl)piperidin-4-yl, 3-hydroxypyrrolidinyl, 3-hydroxypiperidino, 4-hydroxypiperidino, 3,4-dihydroxypiperidino, 4-methoxypiperidino, 4-carboxypiperidino, 4-(hydroxymethyl)piperidino, 2-oxopiperidino, 4-oxopiperidino, 2,2,6,6-tetramethylpiperidino, 2,2,6,6-tetramethyl-4-hydroxypiperidino, 4-methylsulfonylpiperazinyl, 1-oxothiomorpholin-4-yl or 1,1-dioxothiomorpholin-4-yl, and 2-oxazolin-2-yl at Ra22 and Ra23.
The heterocyclic group optionally substituted by(1 to 5 substituent(s) selected from group D is that wherein the above-defined heterocyclic group is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocyclic group. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).
Examples of the group D here include the substituent(s) exemplified for C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.
Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 4-chloropyridin-3-yl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, 2-thienyl, 3-thienyl, furyl, oxazolyl, 2-methyloxazol-4-yl, isoxazolyl, thiazolyl, 2-methylthiazol-4-yl, 2,5-dimethylthiazol-4-yl, 2,4-dimethylthiazol-5-yl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, imidazolidinyl, piperidyl, N-methylpiperidin-4-yl, N-(tert-butoxycarbonyl)piperidin-4-yl, N-acetylpiperidin-4-yl, N-methylsulfonylpiperidin-4-yl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolinyl, benzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl 
and the like.
In addition, the heterocyclic group may be substituted at the 3-, 4-, 5- or 6-position of 2-pyridyl, at the 2-, 4-, 5- or 6-position of 3-pyridyl, at the 2-, 3-, 5- or 6-position of 4-pyridinyl, at the 3-, 4- or 5-position of 2-thienyl, or at the 2-, 4- or 5-position of 3-thienyl, by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl, amino or acetylamino.
At Z and Zxe2x80x2, the heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, 2-oxopyrrolidinyl, 2-oxopiperidyl, pyrazolyl, imidazolyl, 2-imidazolinyl, 2-oxoimidazolidinyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, 2-oxazolinyl, thiazolyl, isothiazolyl, 1,1-dioxoisothiazolidinyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, xcex942-1,2,4-oxadiazolyl, 5-oxo-xcex942-1,2,4-oxadiazolyl, 5-oxo-xcex942-1,2,4-thiadiazolinyl and 2-oxo-3H-1,2,3,5-oxathiadiazolinyl. The group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, xe2x80x94(CH2)txe2x80x94COORa19, xe2x80x94(CH2)txe2x80x94CONRa27Ra28, xe2x80x94(CH2)txe2x80x94ORa20, xe2x80x94(CH2)txe2x80x94NRa29COxe2x80x94Ra24, xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 or xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26.
Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D preferably include piperidino, 4-hydroxypiperidino, 2-oxopiperidin-1-yl, 1-piperazinyl, 1-pyrrolidinyl, 2-oxopyrrolidin-1-yl, morpholino, 4-thiomorpholinyl, 4-tetrahydropyranyl, 3-pyridyl, 2-pyrimidinyl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 5-tetrazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-xcex942-oxazolin-2-yl, 2-thienyl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-xcex942-1,2,4-oxadiazolin-3-yl, 5-oxo-xcex942-1,2,4-thiadiazolin-3-yl and 2-oxo-3H-1,2,3,5-oxathiazolin-4-yl.
Particularly preferably, it is pyridyl, pyrimidinyl, tetrazolyl, thienyl, piperidyl, 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-xcex942-oxazolin-2-yl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-xcex942-1,2,4-oxadiazolin-3-yl, 5-oxo-xcex942-1,2,4-thiadiazolin-3-yl or 2-oxo-3H-1,2,3,5-oxathiadiazolin-4-yl, more preferably 2-oxopyrrolidin-1-yl.
The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group C is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by the 1 to 5 substituent(s) selected from hydroxyl group, the above-defined halogen atom, the above-defined C1-6 alkyl and the above-defined C1-6 alkoxy, which may be unsubstituted. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxyayclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.
The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, particularly preferably cyclohexyl.
At the ring Cy and ring Cyxe2x80x2, the C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group C is preferably cyclopentyl, cyclohexyl, 4-fluorocyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl or 4-methoxycyclohexyl, more preferably cyclopentyl or cyclohexyl, particularly preferably cyclohexyl.
The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkyl. The substituents are selected from the above group B.
Specific examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.
Also exemplified are those wherein cyclopentyl or cyclohexyl is substituted by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.
At cycloalkyl moiety, it is preferably cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. As the C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, it is particularly preferably cyclopropyl, cyclobutyl, cyclohexyl or 4-hydroxycyclohexyl at Ra27 and Ra28.
The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkyl. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).
The group D here includes the substituents recited with regard to C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.
Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.
The group D may be, for example, cyclopentyl or cyclohexyl substituted by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.
The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, and at Z and Zxe2x80x2, it is particularly preferably cyclohexyl.
The optionally substituted C3-8 cycloalkenyl is that wherein the above-defined C3-8 cycloalkenyl is optionally substituted by substituent(s) selected from hydroxyl group, the above-defined halogen atom, the above-defined C1-6 alkyl and the above-defined C1-6 alkoxy, which may be unsubstituted. Examples thereof include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, 4-fluoro-2-cyclohexenyl, 4-methyl-2-cyclohexenyl, 4-methyl-3-cyclohexenyl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, cycloheptenyl and cyclooctenyl and the like, but do not include aryl (e.g., phenyl) or completely saturated cycloalkyl.
The optionally substituted C3-8 cycloalkenyl is particularly preferably cyclohexenyl at the ring Cy.
The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined C6-14 aryl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted arylalkyl. The substituent(s) is(are) selected from the above-mentioned group B.
Examples thereof include benzyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl, 3,5-dichlorobenzyl, pentafluorobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-nitrobenzyl, 4-cyanobenzyl, 4-acetylbenzyl, 4-carboxylbenzyl, 4-carbamoylbenzyl, 4-aminobenzyl, 4-dimethylaminobenzyl, 4-acetylaminobenzyl, 4-(methylsulfonylamino)benzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-methylthiobenzyl, 4-methylsulfonylbenzyl, 4-aminosulfonylbenzyl, 3-nitro-4-methoxybenzyl and 4-nitro-3-methoxybenzyl.
The C6-14 aryl C1-6 alkyl moiety is preferably benzyl or phenethyl, particularly preferably benzyl. The group B is preferably the above-defined halogen atom, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl or xe2x80x94(CH2)rxe2x80x94ORb1. Examples thereof include fluorine atom, chlorine atom, nitro, methyl, tert-butyl, trifluoromethyl, methoxy or trifluoromethyloxy, particularly preferably fluorine atom or chlorine atom.
The specific C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B at Ra12 and Ra13 is preferably benzyl, phenethyl, 3-chlorobenzyl, 4-chloro-3benzyl, 4-tert-butylbenzyl or 3-trifluoromethylbenzyl, it is preferably benzyl at Ra1, Ra19, Ra27, Ra28, Ra31 and Rb5, it is preferably benzyl, phenethyl, 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 4-tert-butylbenzyl or 4-trifluoromethylbenzyl at Ra20, and 4-chlorobenzyl, 3,5-dichlorobenzyl or 4-trifluoromethylbenzyl at Ra22 and Ra23.
It is particularly preferably benzyl at other substituents.
The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C6-14 aryl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).
Examples of group D include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, isopropyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl and dimethylaminosulfonyl.
Examples of C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include benzyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl, 3,5-dichlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl, pentafluorobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-(hydroxymethyl)benzyl, 4-(methoxymethyl)benzyl, 4-(2-carboxylethyl)benzyl, 3-carboxylbenzyl, 4-carboxylbenzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-carbamoylbenzyl, 4-methylthiobenzyl, 4-(dimethylaminocarbonyl)benzyl, 4-methylsulfonylbenzyl, 4-(acetylamino)benzyl, 4-cyanobenzyl, 4-acetylbenzyl, 4-aminobenzyl, 4-dimethylaminobenzyl, 4-(methylsulfonylamino)benzyl, 4-methylsulfinylbenzyl, 4-aminosulfonylbenzyl, (3-nitro-4-methoxyphenyl)methyl and (4-nitro-3-methoxyphenyl)methyl.
At Z and Zxe2x80x2, the C6-14 aryl C1-6 alkyl moiety is preferably benzyl or phenethyl, and the group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, xe2x80x94(CH2)txe2x80x94COORa19, xe2x80x94(CH2)txe2x80x94CONRa27Ra28, xe2x80x94(CH2)txe2x80x94ORa20, xe2x80x94(CH2)txe2x80x94NRa29COxe2x80x94Ra24, xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 or xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26.
The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is preferably benzyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 3,5-dichlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-(hydroxymethyl)benzyl, 4-(methoxymethyl)benzyl, 4-(2-carboxylethyl)benzyl, 3-carboxylbenzyl, 4-carboxylbenzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-carbamoylbenzyl, 4-methylthiobenzyl, 4-(dimethylaminocarbonyl)benzyl, 4-methylsulfonylbenzyl, 4-acetylaminobenzyl, 4-methylsulfinylbenzyl or 4-aminosulfonylbenzyl.
It is particularly preferably the above-defined halogen atom, the above-defined optionally substituted C1-6 alkyl, xe2x80x94(CH2)txe2x80x94COORa19, xe2x80x94(CH2)txe2x80x94CONRa27Ra28, xe2x80x94(CH2)txe2x80x94ORa20 or xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 Examples thereof include fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl and acetylamino. It is more preferably fluorine atom, chlorine atom, methyl, tert-butyl, carboxyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl or methylsulfonyl, most preferably fluorine atom or chlorine atom.
The heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined heterocycle C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocycle C1-6 alkyl. The substituent(s) is(are) selected from the above-mentioned group B.
Examples thereof include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, pyrrolylmethyl, imidazolylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 2-oxazolylmethyl, 5-isothiazolylmethyl, 2-methyloxazol-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 5-thiazolylmethyl, 2-methylthiazol-4-ylmethyl, 2-methylthiazol-5-ylmethyl, 2,5-dimethylthiazol-4-ylmethyl, 4-methylthiazol-2-ylmethyl, 2,4-dimethylthiazol-5-ylmethyl, 2-isothiazolylmethyl, 2-pyrrolinylmethyl, pyrrolidinylmethyl, piperidylmethyl, 4-piperidylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 3-hydroxypyrrolidinylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-acetylpiperidin-4-ylmethyl, 1-methylsulfonylpiperidin-4-ylmethyl, piperazinylmethyl, morpholinomethyl, thiomorpholinylmethyl, 1-tetrahydropyranylmethyl, 2-quinolylmethyl, 1-isoquinolylmethyl and the like.
The heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the alkyl moiety thereof is preferably straight chain alkyl having 1 to 4 carbon atoms. The group B here is preferably the above-defined halogen atom, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, xe2x80x94(CH2)rxe2x80x94COORb1, xe2x80x94(CH2)rCONRb1Rb2 or xe2x80x94(CH2)rxe2x80x94ORb1.
Examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B preferably include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)piperidin-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl and 4-methylthiazol-2-ylmethyl. Particularly preferably, it is 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)piperidin-4-ylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl or 4-methylthiazol-2-ylmethyl at Ra20, 2-pyridylmethyl at Ra22 and Ra23, and 4-pyridylmethyl or 4-methylthiazol-2-ylmethyl at Ra27 and Ra28.
The heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined heterocycle C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocycle C1-6 alkyl. The substituent(s) is(are) selected from the above-mentioned group D (substituents shown under (a) to (q)).
Examples of group D here include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, isopropyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl and dimethylaminosulfonyl.
Examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, pyrrolylmethyl, imidazolylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 2-oxazolylmethyl, 5-isothiazolylmethyl, 2-methyloxazol-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 5-thiazolylmethyl, 2-methylthiazol-4-ylmethyl, 2-methylthiazol-5-ylmethyl, 2,5-dimethylthiazol-4-ylmethyl, 4-methylthiazol-2-ylmethyl, 2,4-dimethylthiazol-5-ylmethyl, 2-isothiazolylmethyl, 2-pyrrolinylmethyl, pyrrolidinylmethyl, piperidylmethyl, 4-piperidylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 2-(4-hydroxypiperidino)ethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-acetylpiperidin-4-ylmethyl, 1-methylsulfonylpiperidin-4-ylmethyl, piperazinylmethyl, morpholinomethyl, thiomorpholinylmethyl, 1-tetrahydropyranylmethyl, 2-quinolylmethyl, 1-isoquinolylmethyl, and the like.
Preferable heterocyclic moiety at Z and Zxe2x80x2 is heterocylic group which is 5-membered or 6-membered monocyclic group. Examples of the heterocyclic moiety include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the alkyl moiety is preferably straight chain alkyl having 1 to 4 carbon atoms, particularly methyl (i.e., methylene).
Preferable group D is the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, xe2x80x94(CH2)txe2x80x94COORa19, xe2x80x94(CH2)txe2x80x94CONRa27Ra28, xe2x80x94(CH2)txe2x80x94ORa20, xe2x80x94(CH2)tNRa29COxe2x80x94Ra24, xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 or xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26.
Preferable examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)piperidin-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl and 4-methylthiazol-2-ylmethyl.
Particularly preferred is 4-hydroxypiperidinomethyl.
The C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B is that wherein the above-defined C3-8 cycloalkyl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkylalkyl. The substituents are selected from the above group B.
Specific examples thereof include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-(cyclopentyl)ethyl, 2-(cyclohexyl)ethyl, cycloheptylmethyl, 4-fluorocyclohexylmethyl, 2-methylcyclopentylmethyl, 3-methylcyclohexylmethyl, 4-methylcyclohexylmethyl, 4,4-dimethylcyclohexylmethyl, 3,5-dimethylcyclohexylmethyl, 4-tert-butylcyclohexylmethyl, 4-hydroxycyclohexylmethyl, 4-methoxycyclohexylmethyl and 2,3,4,5,6-pentafluorocyclohexylmethyl.
Also exemplified are those wherein cyclopentylmethyl or cyclohexylmethyl is substituted by fluorine atom, chlorine atom, bromine atom, nito, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.
At cycloalkyl moiety, it is preferably cyclopentylmethyl or cyclohexylmethyl, and at Ra20, Ra27 and Ra28, it is particularly preferably cyclohexylmethyl.
The carboxyl-protecting group only needs to be suitable for reaction conditions, and is capable of protecting and deprotecting and may be, for example, methyl; substituted methyl group such as methoxymethyl, methylthiomethyl, 2-tetrahydropyranyl, methoxyethoxymethyl, benzyloxymethyl, phenacyl, diacylmethyl, phthalimidomethyl etc.; ethyl; substituted ethyl group such as 2,2,2-trichloroethyl, 2-chloroethyl, 2-(trimethylsilyl)ethyl, 2-methylthioethyl, 2-(p-toluenesulfonyl)ethyl, t-butyl etc.; benzyl; substituted benzyl group such as diphenylmethyl, triphenylmethyl, p-nitrobenzyl, 4-picolyl, p-methoxybenzyl, 2-(9,10-dioxo)anthrylmethyl (etc.; silyl group such as trimethylsilyl, t-butyldimethylsilyl, phenyldimethylsilyl etc.; and the like.
Preferred are industrially effective protecting groups and specifically preferred as Ra36 are methyl and ethyl.
In formula [I], X is preferably 
wherein each symbol is as defined above.
G1, G2, G3 and G4 are each preferably (Cxe2x80x94R1), (Cxe2x80x94R2) (Cxe2x80x94R3) and (Cxe2x80x94R4), G5 is preferably a nitrogen atom, and G6, G8, and G9 are preferably a carbon atom. G7 is preferably C(xe2x80x94R7) or unsubstituted nitrogen atom, wherein R7 is preferably hydrogen atom.
A preferable combination is G2 of (Cxe2x80x94R2) and G6 of a carbon atom, particularly preferably G2 of (Cxe2x80x94R2), G6 of a carbon atom and G5 of a nitrogen atom, most preferably G2 of (Cxe2x80x94R2), G6 of a carbon atom, G5 of a nitrogen atom and G7 of unsubstituted nitrogen atom.
In formulas [I] and [II], 1 to 4 of G1 to G9 in the moiety 
is(are) preferably a nitrogen atom, specifically preferably 
particularly preferably 
more preferably 
most preferably 
It is also a preferable embodiment wherein the 
R1 and R4 are preferably hydrogen atom. R2 is preferably carboxyl, xe2x80x94COORa1, xe2x80x94CONRa2Ra3, xe2x80x94SO2Ra7 (each symbol is as defined above) or heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, particularly preferably carboxyl, xe2x80x94COORa1 or xe2x80x94SO2Ra7, more preferably carboxyl or xe2x80x94COORa1, most preferably carboxyl. R3 is preferably hydrogen atom or xe2x80x94ORa6 (Ra6 is as defined above), particularly preferably hydrogen atom.
Ra1 is preferably optionally substituted C1-6 alkyl.
When R2 is carboxyl or xe2x80x94COORa1, at least one of R1, R3 and R4 is preferably hydroxyl group, halogen atom (particularly fluorine atom, chlorine atom) or xe2x80x94ORa6 (wherein Ra6 is preferably hydrogen atom or methyl).
The ring Cy and ring Cyxe2x80x2 are preferably cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino, particularly preferably cyclopentyl, cyclohexyl or cycloheptyl, more preferably cyclohexyl.
The ring A and ring Axe2x80x2 are preferably phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl or thienyl, particularly preferably phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, more preferably phenyl or pyridyl, and most preferably phenyl.
The ring B and ring Bxe2x80x2 are preferably C1-6 aryl or heterocyclic group, specifically preferably, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or thiadiazolyl, particularly preferably phenyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl or thiazolyl, more preferably, phenyl, pyridyl or thiazolyl, and most preferably phenyl or thiazolyl.
With regard to R5 and R6, one of them is preferably hydrogen atom and the other is halogen atom, particularly fluorine atom. Alternatively, the both are preferably hydrogen atoms. When ring A is phenyl, R5 and R6 preferably are present at an ortho position from G6. The same applies to R5xe2x80x2 and R6xe2x80x2.
Y is preferably xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94, xe2x80x94NHCO2xe2x80x94, xe2x80x94CONHxe2x80x94CHRa14xe2x80x94, xe2x80x94(CH2)mNRa12xe2x80x94(CH2)nxe2x80x94, xe2x80x94CONRa13xe2x80x94(CH2)nxe2x80x94, xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94 or xe2x80x94(CH2)nxe2x80x94NRa12xe2x80x94CHRa15xe2x80x94 (each symbol is as defined above), more preferably, xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94 or xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94, most preferably xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94.
The l, m and n are preferably 0 or an integer of 1 to 4, particularly preferably 0, 1 or 2, at Y. In xe2x80x94(CH2)mxe2x80x94Oxe2x80x94(CH2)nxe2x80x94, m=n=0 or m=0 and n=1 is more preferable, most preferably m=n=0. In xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94, m=n=0, m=0 and n=1, m m=1 and n=1 is more preferable, most preferably m=n=0.
When Y is xe2x80x94Oxe2x80x94(CH2)mxe2x80x94CRa15Ra16xe2x80x94(CH2)nxe2x80x94, Ra16 is preferably hydrogen atom, Ra15 is preferably 
wherein the 
moiety is preferably symmetric. The preferable mode of n, ring B, Z and w and the preferable mode of nxe2x80x2, ring Bxe2x80x2, Zxe2x80x2 and wxe2x80x2 are the same.
When ring A is phenyl, X or Y is preferably present at the para-position relative to G6. When ring B and ring Bxe2x80x2 are phenyl, Z is preferably present at the ortho or meta-position relative to Y. It is preferable that the 3-position on phenyl have one substituent or the 2-position and the 5-position on phenyl each have one substituent.
When ring B is thiazolyl, Y is preferably substituted at the 5-position, and Z is preferably substituted at the 2-position, the 4-position or the 2-position and the 4-position. similarly, when ring Bxe2x80x2 is thiazolyl, (CH2)nxe2x80x94, is also preferably substituted at the 5-position, and Zxe2x80x2 is preferably substituted at the 2-position, the 4-position or the 2-position and the 4-position.
Z and Zxe2x80x2 are preferably group D, xe2x80x9cC6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group Dxe2x80x9d or xe2x80x9cheterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group Dxe2x80x9d, particularly preferably group D or xe2x80x9cC6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group Dxe2x80x9d.
More preferably, they are the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, xe2x80x94(CH2)txe2x80x94COOR19, xe2x80x94(CH2)txe2x80x94CONRa27Ra28, xe2x80x94(CH2)txe2x80x94ORa20, xe2x80x94(CH2)txe2x80x94Ra29COxe2x80x94Ra24, xe2x80x94(CH2)txe2x80x94S(O)qxe2x80x94Ra25 or xe2x80x94(CH2)txe2x80x94SO2xe2x80x94NHRa26, or C6-14 aryl or heterocyclic group optionally substituted by these.
With regard to Z and Zxe2x80x2, the preferable mode of group D that directly substitutes each ring B and ring Bxe2x80x2 and the preferable mode of group D that substitutes C6-14 aryl, C3-8 cycloalkyl, C6-14 aryl C1-6 alkyl or heterocyclic group are the same, wherein they may be the same with or different from each other.
Specific examples of the substituent preferably include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, carbamoylmethoxymethyl, (dimethylaminocarbonyl)methoxymethyl, acetyl, isovaleryl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, hydroxyaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, isobutylaminocarbonyl, tert-butylaminocarbonyl, (4-hydroxybutyl)aminocarbonyl, (1-hydroxypropan-2-yl)aminocarbonyl, (2,3-dihydroxypropyl)aminocarbonyl, (1,3-dihydroxypropan-2-yl)aminocarbonyl, methoxyaminocarbonyl, {2-[2-(methoxy)ethoxy]ethyl}aminocarbonyl, N-ethyl-N-methylaminocarbonyl, N-methyl-N-propylaminocarbonyl, N-isopropyl-N-methylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (2-hydroxy-2-methylpropan-2-yl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isopentyloxy, 2-isopentenyloxy, 3-isohexenyloxy, 4-methyl-3-pentenyloxy, 2-propynyloxy, trifluoromethyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)-methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, N-acetyl-N-methylamino, ureido, isopropylcarbonylamino, isobutylcarbonylamino, tert-butylcarbonylamido, (ethylamino)carbonylamino, (isopropylamino)-carbonylamino, (dimethylamino)carbonylamino, (4-hydroxypiperidino)carbonylamino, [(4-hydroxypiperidinomethyl]-carbonylamino, [(3-hydroxypyrrolidinyl)methyl]carbonylamino, methylsulfonylamino, isopropylsulfonylamino, N-(isopropylsulfonyl)-N-methylamino, methylthio, methylsulfonyl, isopropylsulfonyl, isobutylsulfonyl, methylsulfinyl, isopropylsulfinyl, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl, isopropylaminosulfonyl, tert-butylaminosulfonyl, hydroxyamidino, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-2-fluorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-cyanophenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(2-hydroxyethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 4-(methoxycarbonylmethyl)phenyl, 4-(ethoxycarbonylmethyl)phenyl, 4-acetylphenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-(methoxycarbonyl)phenyl, 4-(ethoxycarbonyl)phenyl, 4-carbamoylphenyl, 4-(methylaminocarbonyl)phenyl, 4-(isopropylaminocarbonyl)phenyl, 4-(dimethylaminocarbonyl)phenyl, 4-(diethylaminocarbonyl)phenyl, 4-[(2-hydroxyethyl)aminocarbonyl]phenyl, 4-[(carboxylmethyl)aminocarbonyl]phenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-ethoxyphenyl, 4-propyloxyphenyl, 4-isopropyloxyphenyl, 4-butyloxyphenyl, 4-isopentyloxyphenyl, 4-(2-isopentenyloxy)phenyl, 4-(3-isohexenyloxy)phenyl, 4-(4-methyl-3-pentenyloxy)phenyl, 4-(2-propynyloxy)phenyl, 4-(trifluoromethyloxy)phenyl, 4-(hydroxymethyloxy)phenyl, 4-(carboxylmethyloxy)phenyl, 4-[(dimethylaminocarbonyl)methyloxy]phenyl, 4-aminophenyl, 4-(methylamino)phenyl, 4-(dimethylaminophenyl), 4-(diethylamino)phenyl, 4-(acetylamino)phenyl, 4-(methylsulfonylamino)phenyl, 4-(methylthio)phenyl, 4-(methylsulfonyl)phenyl, 4-(methylsulfinyl)phenyl, 4-(aminosulfonyl)phenyl, 4-(methylaminosulfonyl)phenyl, 4-(dimethylaminosulfonyl)phenyl, 4-(tert-butylaminosulfonyl)phenyl, tetrazol-5-ylphenyl, cyclohexyl, benzyl, 4-chlorobenzyl, phenethyl, benzyloxy, 4-fluorobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-tert-butylbenzyloxy, 4-trifluoromethylbenzyloxy, phenethyloxy, 2-thienyl, 2-thiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 6-fluoropyridin-3-yl, 5-fluoropyridin-2-yl, 6-chloropyridin-3-yl, 6-methylpyridin-3-yl, 2-pyrimidinyl, 5-tetrazolyl, piperidino, 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-xcex942-oxazolin-2-yl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-xcex942-1,2,4-oxadiazolin-3-yl, 5-oxo-xcex942-1,2,4-thiadiazolin-3-yl, 2-oxo-3H-1,2,3,5-oxathiadiazolin-4-yl, 4-hydroxypiperidinomethyl, piperidinocarbonyl, 4-hydroxypiperidinocarbonyl, 3,4-dihydroxypiperidinocarbonyl, 1-piperazinylcarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl, 4-thiomorpholinylcarbonyl, phenoxy, 2,4-dichlorophenoxy, tetrahydropyranyloxy, 2-pyridylmethyloxy, 3-pyridylmethyloxy, 2-chloropyridin-4-ylmethyloxy, 4-pyridylmethyloxy, 2-piperidylmethyloxy, 3-piperidylmethyloxy, 4-piperidylmethyloxy, 1-methylpiperidin-4-ylmethyloxy, 1-acetylpiperidin-4-ylmethyloxy, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyloxy, 1-(methylsulfonyl)piperidin-4-ylmethyloxy, 2-methylthiazolin-4-yloxy, 2,4-dimethylthiazolin-5-yloxy, dimethylaminocarbonyl-methyloxy, piperidinocarbonylmethyloxy, 4-hydroxypiperidino-carbonylmethyloxy, 2-methylthiazol-4-yl, (2-methylthiazol-4-yl)methyloxy, (2,4-dimethylthiazol-5-yl)methyloxy, benzoyl, 3-fluorobenzoyl, 4-chlorobenzylamino, 3,5-dichlorobenzylamino, 4-trifluoromethylbenzylamino, 2-pyridylmethylamino, benzoylamino, 4-chlorobenzoylamino, 4-trifluoromethylbenzoylamino, 3,5-dichlorobenzoylamino, 3-nitro-4-methoxybenzoylamino, 4-nitro-3-methoxybenzoylamino, 3-pyridylcarbonylamino, morpholinocarbonylamino, 2-oxazolinylamino, 4-hydroxypiperidinosulfony, 1-methylphenylsulfonylamino, 2-thiazolylaminosulfonyl, 2-pyridylaminosulfonyl, benzylaminocarbonyl, N-benzyl-N-methylaminocarbonyl, (4-pyridylmethyl)aminocarbonyl or (cyclohexylmethyl)aminocarbonyl, 2-hydroxyethyloxy, 3-hydroxypropyloxy, 2-methoxyethoxy, 2-(2-methoxyethoxy) ethoxy, azetidinylcarbonyl, 3-hydroxypyrrolidinylcarbonyl, 3-hydroxypiperidinocarbonyl, 4-hydroxypiperidinocarbonyl, 3,4-dihydroxypiperidinocarbonyl, 4-methoxypiperidinocarbonyl, 4-carboxypiperidinocarbonyl, 4-(hydroxymethyl)piperidinocarbonyl, 2-oxopiperidinocarbonyl, 4-oxopiperidinocarbonyl, 2,6-dimethylpiperidinocarbonyl, 2,2,6,6-tetramethylpiperidinocarbonyl, 2,2,6,6-tetramethyl-4-hydroxypiperidinocarbonyl, 1-oxothiomorpholin-4-ylcarbonyl, 1,1-dioxothiomorpholin-4-ylcarbonyl, 1-(methylsulfonyl)piperidin-4-ylaminocarbonyl, 4-methylsulfonylpiperazinylcarbonyl, 4-methylpiperazinylcarbonyl, N,N-bis(2-hydroxyethyl)aminocarbonyl, phenylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclohexylaminocarbonyl, 4-hydroxycyclohexylaminocarbonyl, 4-methylthiazol-2-ylmethylaminocarbonyl, 2-(4-hydroxypiperidino)-ethyloxy, 2-pyridylmethylaminocarbonyl, 3-pyridylmethylaminocarbonyl, N-methyl-N-(4-pyridylmethyl)aminocarbonyl, cyclohexylmethyloxy, 4-hydroxypiperidinocarbonylmethyloxy and 4-methylthiazol-2-ylmethyloxy.
Particularly preferable examples of the substituent include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, hydroxymethyl, carboxyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxylethyl)aminocarbonyl, (carboxymethyl)aminocarbonyl, methoxy, 2-isopentenyloxy, 2-propynyloxy, methylthio, methylamino, dimethylamino, acetylamino, methylsulfonylamino, methylsulfonyl, aminosulfonyl, dimethylaminosulfonyl, tert-butylaminosulfonyl, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 4-(methoxymethyl phenyl, 4-(2-hydroxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, benzyl, phenethyl, benzyloxy, 4-fluorobenzyloxy, 4-chlorobenzyloxy, 2-thiazolyl, 3-pyridyl, 4-pyridyl, 4-pyridylmethyloxy, 2.-piperidylmethyloxy, 3-piperidylmethyloxy, 4-piperidylmethyloxy, 1-methylpiperidin-4-ylmethyloxy, 1-acetylpiperidin-4-ylmethyloxy, 2-chloropiperidin-4-ylmethyloxy, 1-(methylsulfonyl)piperidin-4-ylmethyloxy, 2-methylthiazol-4-yl, (2-methylthiazol-4-yl)methyloxy, (2,4-dimethylthiazol-5-yl)methyloxy, 5-tetrazolyl, 3-fluorobenzoyl, piperidinocarbonyl, 4-hydroxylpiperidinocarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl, 4-thiomorpholinylcarbonyl, benzylaminocarbonyl, N-benzyl-N-methylaminocarbonyl, (4-pyridylmethyl)aminocarbonyl and (cyclohexylmethyl)aminocarbonyl.
Most preferable substituents are fluorine atom, chlorine atom, methyl, hydroxymethyl, carboxyl, carbamoyl, methylaminocarbonyl, dimethylaminocarbonyl, methoxy, methylamino, acetylamino, aminosulfonyl, dimethylaminosulfonyl, tert-butylaminosulfonyl, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl and 2-oxopyrrolidin-1-yl.
The w is preferably 1 or 2, r and t are preferably 0, 1 or 2, particularly preferably 0 or 1, more preferably 0, p is preferably 1, and q is preferably 0 or 2.
In formula [I], when X is 
wherein each symbol is as defined above and w is 2 or above, one of Z is preferably C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D, particularly preferably C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.
The pharmaceutically acceptable salt may be any as long as it forms a non-toxic salt with a compound of the above-mentioned formula [I] or [II]. Such salt can be obtained by reacting the compound with an inorganic acid, such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and the like, or an organic acid, such as oxalic acid, malonic acid, citric acid, fumaric acid, lactic acid, malic acid, succinic acid, tartaric acid, acetic acid, trifluoroacetic acid, gluconic acid, ascorbic acid, methylsulfonic acid, benzylsulfonic acid and the like, or an inorganic base, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonium hydroxide and the like, or an organic base, such as methylamine, diethylamine, triethylamine, triethanolamine, ethylenediamine, tris(hydroxymethyl)methylamine, guanidine, choline, cinachonine and the like, with an amino acid, such as lysine, arginine, alanine and the like. The present invention encompasses water-retaining product, hydrate and solvate of each compound.
The compounds of the above-mentioned formula [I] or [II] have various isomers. For example, E compound and Z compound are present as geometric isomers, and when the compound has an asymmetric carbon, an enantiomer and a diastereomer are present due to the asymmetric carbon. A tautomer may be also present. The present invention encompasses all of these isomers and mixtures thereof.
The present invention also encompasses prodrug and metabolite of each compound.
A prodrug means a derivative of the compound of the present invention, which is capable of chemical or metabolic decomposition, which shows inherent efficacy by reverting to the original compound after administration to a body, and which includes salts and complexes without a covalent bond.
When the inventive compound is used as a pharmaceutical preparation, the inventive compound is generally admixed with pharmaceutically acceptable carriers, excipients, diluents, binders, disintegrators, stabilizers, preservatives, buffers, emulsifiers, aromatics, coloring agents, sweeteners, thickeners, correctives, solubilizers, and other additives such as water, vegetable oil, alcohol such as ethanol, benzyl alcohol and the like, polyethylene glycol, glycerol triacetate, gelatin, lactose, carbohydrate such as starch and the like, magnesium stearate, talc, lanolin, petrolatum and the like, and prepared into a dosage form of tablets, pills, powders, granules, suppositories, injections, eye drops, liquids, capsules, troches, aerosols, elixirs, suspensions, emulsions, syrups and the like, which can be administered systemically or topically and orally or parenterally.
While the dose varies depending on the age, body weight, general condition, treatment effect, administration route and the like, it is from 0.1 mg to 1 g for an adult per dose, which is given one to several times a day.
The prophylaxis of hepatitis C means, for example, administration of a pharmaceutical agent to an individual found to carry an HCV by a test and the like but without a symptom of hepatitis C, or to an individual who shows an improved disease state of hepatitis after a treatment of hepatitis C, but who still carries an HCV and is associated with a risk of recurrence of hepatitis.
Inasmuch as HCV is known to be a virus associated with many genetic mutations, a compound effective for many genotypes is one of the preferable modes. If a compound ensures high blood concentration when administered as a pharmaceutical agent to an animal infected with HCV, it is also one of the preferable modes. From these aspects, a compound having high inhibitory activity on both HCV type 1a and type 1b and high blood concentration, such as 2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, is particularly preferable.
The fused ring compound of the formula [I] or [II] of the present invention can be administered to mammals inclusive of human for the purpose of prevention or treatment of hepatitis C or inhibition of hepatitis C virus polymerase. The fused ring compound of the present invention can be also administered to mammals inclusive of human along with at least one pharmaceutical agent (hereinafter combination drug) selected from an antiviral agent other than the compound of the formula [I], an antiinflammatory agent and an immunostimulant for the purpose of prevention or treatment of hepatitis C or inhibition of hepatitis C virus polymerase. In the case of combined administration, the compound of the present invention can be administered simultaneously with the combination drug or administered at certain time intervals. In the case of combined administration, a pharmaceutical composition containing the compound of the present invention and a combination drug can be administered. Alternatively, a pharmaceutical composition containing the compound of the present invention and a pharmaceutical composition containing a combination drug may be administered separately. The administration route may be the same or different.
In the case of a combined administration, the compound of the present invention can be administered once a day or several times a day in a single dose of 0.1 mg to 1 g, or may be administered in a smaller dose. The combination drug can be administered in a dose generally used for the prevention or treatment of hepatitis C or in a smaller dose.
Examples of other antiviral agent include interferons (interferon xcex1, interferon xcex2, interferon xcex3 etc.), Ribavirin (1-xcex2-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) and the like.
Examples of the production method of the compound to be used for the practice of the present invention are given in the following. However, the production method of the compound of the present invention is not limited to these examples.
Even if no directly corresponding disclosure is found in the following Production Methods, the steps may be modified for efficient production of the compound, such as introduction of a protecting group into a functional group with deprotection in a subsequent step, and changing the order of Production Methods and steps.
The treatment after reaction in each step may be( conventional ones, for which typical methods, such as isolation and purification, crystallization, recrystallization, silica gel chromatography, preparative HPLC and the like, can be appropriately selected and combined.
Production Method 1
In this Production Method, a benzimidazole compound is formed from a nitrobenzene compound.
Production Method 1-1
wherein Hal is halogen atom, such as chlorine atom, bromine atom and the like, Rc1 is halogen atom, such as chlorine atom, bromine atom and the like, or hydroxyl group, and other symbols are as defined above.
Step 1
A compound [1] obtained by a conventional method or a commercially available compound [1] is reacted with amine compound [2] in a solvent such as N,N-dimethylformamide (DMF), acetonitrile, tetrahydrofuran (THF), toluene and the like in the presence or absence of a base such as potassium carbonate, triethylamine, potassium t-butoxide and the like at room temperature or with heating to give compound [3].
Step 2
The compound [3] is hydrogenated in a solvent such as methanol, ethanol, THF, ethyl acetate, acetic acid, water and the like in the presence of a catalyst such as palladium carbon, palladium hydroxide, platinum oxide, Raney nickel and the like at room temperature or with heating to give compound [4]. In addition, compound [3] is reduced with a reducing agent such as zinc, iron, tin(II) chloride, sodium sulfite and the like, or reacted with hydrazine in the presence of iron(III) chloride to give compound [4].
Step 3
The compound [4] is condensed with carboxylic acid compound [5] in a solvent such as DMF, acetonitrile, THF, chloroform, ethyl acetate, methylene chloride, toluene and the like using a condensing agent such as dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, diphenylphosphoryl azide and the like and, where necessary, adding N-hydroxysuccinimide, 1-hydroxybenzotriazole and the like to give amide compound [6]. Alternatively, amide compound [6] can be obtained from compound [5] as follows. The carboxylic acid compound [5] is converted to an acid halide derived with thionyl chloride, oxalyl chloride and the like, or an active ester (e.g., mixed acid anhydride derived with ethyl chlorocarbonate and the like), which is then reacted in the presence of a base, such as triethylamine, potassium carbonate, pyridine and the like, or in an amine solvent, such as pyridine and the like, to give amide compound [6].
Step 4
The compound [6] is heated in a solvent such as ethanol, methanol, toluene, DMF, chloroform and the like or without a solvent in the presence of an acid such as acetic acid, formic acid, hydrochloric acid, dilute sulfuric acid, phosphoric acid, polyphosphoric acid, p-toluenesulfonic acid and the like, a halogenating agent such as zinc chloride, phosphorus oxychloride, thionyl chloride and the like or acid anhydride such as acetic anhydride and the like, to allow cyclization to give compound [I-2].
Production Method 1-2
This Production Method is an alternative method for producing compound [I-2]. 
wherein each symbol is as defined above.
Step 1
The compound [3] obtained in the same manner as in Step 1 of Production Method 1-1 is subjected to amide condensation with compound [5] in the same manner as in Step 3 of Production Method 1-1 to give compound [7].
Step 2
The compound [7] is reduced in the same manner as in Step 2 of Production Method 1-1 to give compound [8].
Step 3
The compound [8] is subjected to cyclization in the same manner as in Step 4 of Production Method 1-1 to give compound [I-2].
Production Method 1-3
wherein Rc2 is alkyl such as methyl, ethyl and the like, and other symbols are as defined above.
The compound [4] is reacted with imidate compound. [9] in a solvent such as methanol, ethanol, acetic acid, DMF, THF, chloroform and the like at room temperature or with heating to give compound [I-2].
In addition, compound [4] may be reacted with aldehyde compound [10] in a solvent such as acetic acid, formic acid, acetonitrile, DMF, nitrobenzene, toluene and the like in the presence or absence of an oxidizing agent such as benzofuroxan, manganese dioxide, 2,3-dichloro-5,6-dicyano-p-benzoquinone, iodine, potassium ferricyanide and the like with heating to give compound [I-2].
Alternatively, compound [4] and carboxylic acid compound [11] may be heated to allow reaction in the presence of polyphosphoric acid, phosphoric acid, phosphorus oxychloride, hydrochloric acid and the like to give compound [I-2].
Production Method 2
In this Production Method, conversion of the substituents (R1, R2, R3, R4) on the benzene ring of benzimidazole is shown. While a method of converting R2 when R1, R3 and R4 are hydrogen atoms is shown, this Production Method is applicable irrespective of the position of substitution.
Production Method 2-1
Conversion of Carboxylic Acid Ester Moiety to Amide 
wherein E is a single bond, xe2x80x94(CH2)sxe2x80x94, xe2x80x94Oxe2x80x94(CH2)sxe2x80x94 or xe2x80x94NHxe2x80x94(CH2)sxe2x80x94 (wherein s is an integer of 1 to 6), Rc3, Rc4 and Rc5 are C1-6alkyl, and other symbols are as defined above.
Step 1
The compound [I-2-1] obtained in the same manner as in the above-mentioned Production Method is subjected to hydrolysis in a solvent such as methanol, ethanol, THF, dioxane and the like, or in a mixed solvent of these solvents and water under basic conditions with sodium hydroxide, potassium hydroxide, potassium carbonate, lithium hydroxide and the like or under acidic conditions with hydrochloric acid, sulfuric acid and the like to give compound [I-2-2].
Step 2
The compound [I-2-2] is reacted with compound [12] in the same manner as in Step 3 of Production Method 1-1 to give compound [I-2-3].
Production Method 2-2
Conversion of Cyano Group to Substituted Amidino Group 
wherein each symbol is as defined above.
The compound [I-2-4] obtained in the same manner as in the above-mentioned Production Method is reacted with hydroxylamine in a solvent such as water, methanol, ethanol, THF, DMF and the like to give compound [I-2-5]. When a salt of hydroxylamine such as hydrochloride and the like is used, the reaction is carried out in the presence of a base such as sodium hydrogencarbonate, sodium hydroxide, triethylamine and the like.
Production Method 2-3
Conversion of Sulfonic Acid Ester Moiety to Sulfonic Acid 
wherein Rc6 is C1-6alkyl, and other symbols are as defined above.
The compound [I-2-6] obtained in the same manner as in the above-mentioned Production Method is reacted with iodide salt such as sodium iodide, lithium iodide and the like, bromide salt such as sodium bromide, trimethylammonium bromide and the like, amine such as pyridine, trimethylamine, triazole and the like, phosphine such as triphenylphosphine and the like in a solvent such as DMF, dimethyl sulfoxide (DMSO), acetonitrile, methanol, ethanol, water and the like with heating to give compound [I-2-7].
Production Method 3
This Production Method relates to convertion of the substituent(s) on phenyl group at the 2-position of benzimidazole. This Production Method can be used even when phenyl is a different ring.
Production Method 3-1
Conversion of Hydroxyl Group to Ether 
wherein Rc7 is optionally substituted alkyl corresponding to Ra11, G1 is a single bond, *xe2x80x94(CH2)nxe2x80x94, *xe2x80x94(CH2)nxe2x80x94Oxe2x80x94, *xe2x80x94(CH2)nxe2x80x94COxe2x80x94 or *xe2x80x94(CH2)mxe2x80x94CRa15Ra16)xe2x80x94(CH2)nxe2x80x94, wherein * show the side to be bonded to Rc1, and other symbols are as defined above.
When Rc1 of compound [13] is halogen atom, compound [I-2-8] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [13] in a solvent such as DMF, DMSO, acetonitrile, ethanol, THF and the like in the presence of a base such as sodium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium ethoxide, potassium t-butoxide and the like at room temperature or with heating to give compound [II-2-1].
When Rc1 of compound [13] is hydroxyl group, the hydroxyl group of compound [13] is converted to halogen atom with thionyl chloride, phosphorus tribromide, carbon tetrabromide-triphenylphosphine and the like and reacted with compound [I-2-8] by the aforementioned method to give compound [II-2-1]. In this case, compound [I-2-8] may be subjected to Mitsunobu reaction with compound [13] in a solvent such as DMF, acetonitrile, THF and the like using triphenylphosphine-diethyl azodicarboxylate and the like to give compound [II-2-1].
The compound [I-2-9] can be obtained in the same manner from compound [I-2-8] and compound [14].
Production Method 3-2
Conversion of Nitro to Substituted Amino Group 
wherein Rc8 is C16alkyl, G2 is *xe2x80x94(CH2)nxe2x80x94 or *xe2x80x94CHRa15, G3 is xe2x80x94COxe2x80x94, *xe2x80x94CO2xe2x80x94, *xe2x80x94CONH or xe2x80x94SO2xe2x80x94, and other symbols are as defined above.
Step 1
The nitro compound [I-2-10] obtained in the same manner as in the above-mentioned Production Method is reacted in the same manner as in Step 2 of Production Method 1-1 to give compound [I-2-11].
Step 2
The compound [I-2-11] is alkylated with compound [15] in the same manner as in Production Method 3-1 to give compound [II-2-2].
Step 3
When G3 of compound [16] is xe2x80x94COxe2x80x94, xe2x80x94CO2xe2x80x94 or xe2x80x94CONHxe2x80x94, compound [I-2-11] is acylated with compound [16] in the same manner as in Step 3 of Production Method 1-1 to give compound [II-2-3].
When G3 of compound [16] is xe2x80x94SO2xe2x80x94, sulfonylation is conducted using sulfonyl halide instead of acid halide used in Step 3 of Production Method 1-1 to give compound [II-2-3].
The compound [I-2-11] is acylated with compound [17] in the same manner as above to give compound [I-2-12].
This Production Method is applied in the same manner as above to give disubstituted compounds (tertiary amine) of compound [II-2-2], compound [II-2-3] and compound [I-2-12].
Production Method 3-3
Conversion of Carboxylic Acid Ester Moiety to Amide 
wherein Rc9 is C1-6 alkyl, G4is #xe2x80x94(CH2)nxe2x80x94, #xe2x80x94(CH2)xe2x80x94NHxe2x80x94 or #xe2x80x94CHRa14xe2x80x94 wherein # shows the side that is bounded to amine and other symbols are as defined above.
Step 1
The compound [I-2-13] obtained in the same manner as in the above-mentioned Production Method is reacted in the same manner as in Step 1 of Production Method 2-1 to give compound [I-2-14].
Step 2
The compound [I-2-14] is reacted with compound [18] in the same manner as in Step 2 of Production Method 2-1 to give compound [II-2-4].
The compound [I-2-15] is obtained from compound [I-2-14] and compound [19] in the same manner as above.
Production Method 4
In this Production Method, additional substituent.(s) is(are) introduced into ring B on phenyl group that substitutes the 2-position of benzimidazole. This Production Method is applicable even when phenyl is a different ring.
Production Method 4-1
Direct Bonding of Ring Zxe2x80x3 to Ring B 
wherein ring Zxe2x80x3xe2x80x94M is aryl metal compound, ring Zxe2x80x3 moiety is optionally substituted C6-14 aryl or optionally substituted heterocyclic group corresponding to substituent Z, and the metal moiety contains boron, zinc, tin, magnesium and the like, such as phenylboronic acid, wxe2x80x3 is 0, 1 or 2, and other symbols are as defined above.
The compound [II-2-5] obtained in the same manner as in the above-mentioned Production Method is reacted with aryl metal compound [20] in a solvent such as DMF, acetonitrile, 1,2-dimethoxyethane, THF, toluene, water and the like in the presence of a palladium catalyst such as tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium(II) dichloride, palladium acetate-triphenylphosphine and the like, a nickel catalyst such as nickel chloride, [1,3-bis(diphenylphosphino)propane] nickel(II) chloride and the like, and a base such as potassium carbonate, potassium hydrogencarbonate, sodium hydrogen-carbonate, potassium phosphate, triethylamine and the like at room temperature or with heating, to give compound [II-2-6].
Production Method 4-2
Conversion of Hydroxyl Group to Ether 
wherein Rc10 is xe2x80x94Ra20 or xe2x80x94(CH2)pxe2x80x94CORa21 corresponding to substituent Z, and other symbols are as defined above.
The compound [II-2-7] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [21] in the same manner as in Production Method 3-1 to give compound [II-2-8].
Production Method 4-3
Synthesis in Advance of Ring B Part Such as Compound [13] in Production Method 3-1
wherein Rc11 is leaving group such as bromine atom, iodine atom, trifluoromethanesulfonyloxy and the like, Rc12 is formyl, carboxyl or carboxylic acid ester such as methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl and the like, and other symbols are as defined above.
Step 1
Commercially available compound [22] or compound [22] obtained by a conventional method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-l to give compound [23].
Step 2
The compound [23] obtained in the same manner as in the above-mentioned Production Method is reduced according to a conventional method to give compound [24].
For example, compound [23] is reacted with in a solvent such as methanol, ethanol, THF and the like in the presence of a reducing agent such as lithium aluminum hydride, sodium borohydride and the like under cooling to heating to give compound [24].
Step 3
The compound [24] obtained in the same manner as in the above-mentioned Production Method is reacted in a solvent such as 1,4-dioxane, diethyl ether, THF, dichloromethane, chloroform, toluene and the like with a halogenating agent, such as phosphorus pentachloride, phosphorus tribromide, thionyl chloride and the like, in the presence of a tertiary amine such as pyridine and the like to give compound [25].
Step 4
The compound [24] or [25] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [I-2-8] in the same manner as in Production Method 3-1 to give compound [II-2-9].
Production Method 4-4
wherein Mxe2x80x2 is a metal such as magnesium, lithium, zinc and the like, and other symbols are as defined above.
Step 1
Commercially available compound [41] or compound [41] obtained by a conventional method is converted to aryl metal reagent by a conventional method to give compound [42].
For example, when Mxe2x80x2 is magnesium, magnesium is reacted with compound [41] in a solvent such as THF, diethyl ether, benzene, toluene and the like, preferably THF, from cooling to heating preferably at xe2x88x92100xc2x0 C. to 100xc2x0 C. to give compound [42].
Step 2
The compound [42] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [43] to give compound [44].
The compound [42] is reacted in a solvent such as diethyl ether, benzene, toluene, THF and the like, preferably THF, from cooling to room temperature, preferably at xe2x88x92100xc2x0 C. to 30xc2x0 C. to give compound [44].
Step 3
The compound [44] obtained in the same manner as in the above-mentioned Production Method is halogenated in the same manner as in Step 3 of Production Method 4-3 to give compound [45].
The compound [44] is reacted with thionyl chloride and pyridine preferably in toluene solvent to give compound [45].
When compound [45] is symmetric, namely, when the ring B-(Z)w moiety and the ring Bxe2x80x2-(Zxe2x80x2)wxe2x80x2 moiety are the same, compound [42] is reacted with formate such as methyl formate, ethyl formate and the like, preferably ethyl formate, in a solvent such as diethyl ether, benzene, toluene, THF and the like, )preferably THF, from cooling to room temperature, preferably at xe2x88x92100xc2x0 C. to 30xc2x0 C., to give compound [45].
Production Method 4-5
Method Including Steps to Introduce a Protecting Group into a Functional Group 
wherein Rc13 is carboxylic acid protecting group such as tert-butyl and the like, Rc14 is carboxylic acid protecting group such as methyl and the like and other symbols are as defined above.
Step 1
Commercially available compound [26] or compound. [26] obtained by a conventional method is protected by a conventional method to give compound [27].
For example, when Rc13 is tert-butyl, compound [26] is converted to acid halide with thionyl chloride, oxalyl chloride and the like in a solvent such as THF, chloroform, dichloromethane, toluene and the like, and reacted with potassium tert-butoxide to give compound [27].
As used herein, Rc13 may be a different protecting group as long as it is not removed during the Step 2 or Step 3 but removed in Step 4 without affecting xe2x80x94CO2Rc14.
Step 2
The methyl group of compound [27] obtained in the same manner as in the above-mentioned Production Method is Converted to bromomethyl with N-bromosuccinimide and N,Nxe2x80x2-azobisisobutyronitrile and reacted with compound [I-2-1-16] in the same manner as in Production Method 3-1 to give compound [II-2-10].
Step 3
The compound [II-2-10] obtained in the same manner as in the above-mentioned Production Method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-1 to give compound [II-2-11].
Step 4
The Rc13 of the compound [II-2-11] obtained in the same manner as in the above-mentioned Production Method is removed by a conventional method to give compound [II-2-12].
The protecting group of carboxylic acid can be removed by a conventional deprotection method according to the protecting group. In this Step, the conditions free from reaction of Rc14 are preferable. For example, when Rc13 is tert-butyl, compound [II-2-11] is treated with trifluoroacetic acid in a solvent such as dichloromethane, chloroform and the like to give compound [II-2-12].
Step 5
The compound [II-2-12] obtained in the same manner as in the above-mentioned Production Method is subjected to amide condensation with compound [28] in the same manner as in Step 3 of Production Method 1-1 to give compound [II-2-13].
Step 6
The compound [II-2-13] obtained in the same manner as in the above-mentioned Production Method is deprotected in the same manner as in Step 1 of Production Method 2-1 to give compound [II-2-14].
As used herein, Rc14 is preferably a protecting group that does not react during the Step 1 through Step 5 but removed in this Step.
For example, when Rc14 is methyl, compound [II-2-13] is reacted in an alcohol solvent such as methanol, ethanol, n-propanol, isopropanol and the like or a mixed solvent of alcohol solvent and water in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide and the like from cooling to heating for deprotection, followed by acidifying the reaction solution to give compound [II-2-14].
Production Method 4-6
wherein g is an integer of 1 to 5, and other symbols are as defined above.
Step 1
The compound [I-2-16] obtained by the above-mentioned Production Method is reacted with toluene derivative [41] in the same manner as in Step 2 of Production Method 4-5 to give compound [II-2-17].
Step 2
The compound [II-2-17] obtained by the above-mentioned Production Method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-1 to give compound [II-2-18].
Step 3
The compound [II-2-18] obtained by the above-mentioned Production Method is reduced in the same manner as in ;Step 2 of Production Method 1-1 to give compound [II-2-19].
Step 4
The compound [II-2-19] obtained by the above-mentioned Production Method is amide condensed with compound [42] in the same manner as in Step 3 of Production Method 1-1 and subjected to cyclization in the same manner as in Step 1 of Production Method 1-1 to give compound [II-2-20].
Step 5
The compound [II-2-20] obtained by the above-mentioned Production Method is hydrolyzed in the same manner as in Step 1 of Production Method 2-1 to give compound [II-2-21].
Production Method 5
Formation of Indole Ring 
wherein Rc15 is protecting group such as trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl and the like, andother symbols are as defined above.
Step 1
The compound [29] obtained in the same manner as in the above-mentioned Production Method or conventional method is reacted with compound [30] in a solvent such as DMF, acetonitrile, 1,2-dimethoxyethane, THF, toluene, water and the like using a palladium catalyst such as tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium(II) dichloride, palladium acetate-triphenylphosphine and the like, a copper catalyst such as copper(I) iodide and the like or a mixture thereof, and in the presence of a base such as potassium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate, potassium phosphate, triethylamine and the like to give compound [31].
Step 2
The compound [31] obtained in the same manner as in the above-mentioned Production Method is reacted in an alcohol solvent such as methanol, ethanol and the like or a mixed solvent of an alcohol solvent and a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, methylene chloride, toluene and the like in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydride, sodium hydride, potassium hydride and the like at room temperature or with heating for deprotection, and reacted with compound [32] obtained in the same manner as in Step 1 of Production Method 1-1 in the same manner as in Step 1 of Production Method 5 to give compound [33].
Step 3
The compound [33] obtained in the same manner as in the above-mentioned Production Method was subjected to cyclization in a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, methylene chloride, toluene and the like in the presence of a copper catalyst such as copper(I) iodide and the like or a palladium catalyst such as palladium(II) chloride and the like at room temperature or with heating to give compound [II-2-15].
Production Method 6
Formation of imidazo[1,2-a]pyridine Ring 
wherein Rc16 and Rc17 are each independently alkyl, such as methyl, ethyl and the like, and other symbols are as defined above.
Step 1
The compound [34] obtained by the above-mentioned Production Method or a conventional method is subjected to amide condensation with compound [35] in the same manner as in Step 3 of Production Method 1-1 to give compound [36].
Step 2
The compound [36] obtained by the above-mentioned Production Method is reacted with Grignard reagent [37] obtained by a conventional method to give compound [38].
Alternatively, an acid halide of compound [34] may be used instead of compound [36].
Step 3
The compound [38] obtained by the above-mentioned Production Method is subjected to halogenation by a conventional method to give compound [39].
For example, when Hal is a bromine atom, compound [38] is reacted with bromine under cooling or at room temperature in a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, toluene and the like to give compound [39].
Alternatively, a halogenating agent such as hypohalite (e.g., hypochlorite and the like), N-bromosuccinimide and the like may be used instead of bromine for halogenation.
Step 4
The compound [39] obtained by the above-mentioned Production Method is subjected to cyclization with compound [40] obtained by a conventional or known method (JP-A-8-48651) in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydride, sodium hydride, potassium hydride and the like in a solvent or without a solvent at room temperature or with heating to give compound [II-2-16].
In the compounds of the formulas [I] and [II], a desired heterocyclic group can be formed according to a method similar to the methods disclosed in known publications. Examples of such heterocyclic group and reference publications are recited in the following.
5-oxo-xcex942-1,2,4-oxadiazolin-3-yl (or 2,5-dihydro-5-oxoxe2x80x944H-1,2,4-oxadiazol-3-yl), 5-oxo-xcex942-1,2,4-thiadiazolin-3-yl (or 2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl), 2-oxo-xcex943-1,2,3,5-oxathiadiazolin-4-yl (or 2-oxo-xcex943-1,2,4-oxathiadiazol-4-yl): Journal of Medicinal Chemistry, 39(26), 5228-35, 1996,
5-oxo-xcex942-1,2,4-triazolin-3-yl: J Org Chem, 61(24), 839)7-8401, 1996,
1-oxo-xcex943-1,2,3,5-thiatriazolin-4-yl: Liebigs Ann Chem, 1376, 1980,
3-oxo-xcex944-1,2,4-oxadiazolin-5-yl: EP145095,
5-oxo-xcex942-1,3,4-oxadiazolin-2-yl: J Org Chem, 20, 412, 1955,
5-oxo-xcex943-1,2,4-dioxazolin-3-yl: J Prakt Chem, 314, 145, 1972,
3-oxo-xcex944-1,2,4-thiadiazolin-5-yl: JP-A-61-275271,
5-oxo-xcex943-1,2,4-dithiazolin-3-yl: J Org Chem, 61(19), 6639-6645, 1996,
2-oxo-xcex944-1,3,4-dioxazolin-5-yl: J Org Chem, 39, 2472, 1974,
2-oxo-xcex944-1,3,4-oxathiazolin-5-yl: J Med Chem, 35(20), 3691-98, 1992,
5-oxo-xcex942-1,3,4-thiadiazolin-2-yl: J Prakt Chem, 332(1), 55, 1990,
5-oxo-xcex942-1,4,2-oxathiazolin-3-yl: J Org Chem, 31, 2417, 1966,
2-oxo-xcex944-1,3,4-dithiazolin-5-yl: Tetrahedron Lett, 23, 5453, 1982,
2-oxo-xcex944-1,3,2,4-dioxathiazolin-5-yl: Tetrahedron Lett:, 319, 1968,
3,5-dioxoisooxazolidin-4-yl: Helv Chim Acta, 1973, 48, 1965,
2,5-dioxoimidazolidin-4-yl: Heterocycles, 43(1), 49-5(1), 1996,
5-oxo-2-thioxoimidazolidin-4-yl: Heterocycles, 5, 391, 1983,
2,4-dioxooxazolidin-5-yl: J Am Chem Soc, 73, 4752, 1951,
4-oxo-2-thioxooxazolidin-5-yl: Chem Ber, 91, 300, 19513,
2,4-dioxothiazolidin-5-yl: JP-A-57-123175,
4-oxo-2-thioxothiazolidin-5-yl: Chem Pharm Bull, 30, :3563, 1982,
The Production Methods shown in the above-mentioned Production Methods 2 to 4 can be used for the synthesis of compounds other than benzimidazole of the formulas [I] and [II], such as compounds [II-2-15] and [II-2-16].
The compounds of the formulas [I], [II] and [III], 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and 4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole and production methods thereof of the present invention are explained in detail in the following by way of Examples. It is needless to say that the present invention is not limited by these Examples.